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553 results on '"Nieminen,MS"'

1. Drug–gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval

Author: Avery, CL, Sitlani, CM, Arking, DE, Arnett, DK, Bis, JC, Boerwinkle, E, Buckley, BM, Ida Chen, Y-D, de Craen, AJM, Eijgelsheim, M, Enquobahrie, D, Evans, DS, Ford, I, Garcia, ME, Gudnason, V, Harris, TB, Heckbert, SR, Hochner, H, Hofman, A, Hsueh, W-C, Isaacs, A, Jukema, JW, Knekt, P, Kors, JA, Krijthe, BP, Kristiansson, K, Laaksonen, M, Liu, Y, Li, X, MacFarlane, PW, Newton-Cheh, C, Nieminen, MS, Oostra, BA, Peloso, GM, Porthan, K, Rice, K, Rivadeneira, FF, Rotter, JI, Salomaa, V, Sattar, N, Siscovick, DS, Slagboom, PE, Smith, AV, Sotoodehnia, N, Stott, DJ, Stricker, BH, Stürmer, T, Trompet, S, Uitterlinden, AG, van Duijn, C, Westendorp, RGJ, Witteman, JC, Whitsel, EA, and Psaty, BM
Subjects: Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Human Genome, Genetics, Patient Safety, 5.1 Pharmaceuticals, Good Health and Well Being, Computer Simulation, Cross-Sectional Studies, Drug-Related Side Effects and Adverse Reactions, Electrocardiography, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Linear Models, Long QT Syndrome, Markov Chains, Pharmacogenetics, Polymorphism, Single Nucleotide, Quantitative Trait, Heritable, White People, gene-environment interaction, genetic epidemiology, QT interval, Pharmacology & Pharmacy, Pharmacology and pharmaceutical sciences
Abstract: Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the 'missing heritability' of complex traits. Here, we describe four independent analyses in 33 781 participants of European ancestry from 10 cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%) and QT-prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable-adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-single-nucleotide polymorphism (SNP) interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0 × 10(-8)). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.
Published: 2014

2. Soluble triggering receptor expressed on myeloid cells-1 is a marker of organ injuries in cardiogenic shock: results from the CardShock Study

Author: Kimmoun, A, Duarte, K, Harjola, VP, Tarvasmaki, T, Levy, B, Mebazaa, A, Gibot, S, Koniari, K, Voumvourakis, A, Karavidas, A, Parissis, J, Sans-Rosello, J, Vila, M, Duran-Cambra, A, Sionis, A, Parenica, J, Stipal, R, Ludka, O, Palsuva, M, Ganovska, E, Kubena, P, Spinar, J, Lindholm, MG, Hassager, C, Kober, L, Backlund, T, Lassus, J, Jurkko, R, Tolppanen, H, Nieminen, MS, Jarvinen, K, Nieminen, T, Pulkki, K, Soininen, L, Sund, R, Tierala, I, Tolonen, J, Varpula, M, Korva, T, Pietila, M, Pitkala, A, Marino, R, Di Somma, S, Metra, M, Bulgari, M, Lazzarini, V, Carubelli, V, Sousa, A, Silva-Cardoso, J, Sousa, C, Paiva, M, Rangel, I, Almeida, R, Pinho, T, Maciel, MJ, Banaszewski, M, Stepinska, J, Skrobisz, A, Goral, P, Zeymer, U, and Thiele, H
Subjects: Cardiogenic Shock, STREM, Biomarkers, Outcome
Abstract: Aims Optimal outcome after cardiogenic shock (CS) depends on a coordinated healing response in which both debris removal and extracellular matrix tissue repair play a crucial role. Excessive inflammation can perpetuate a vicious circle, positioning leucocytes as central protagonists and potential therapeutic targets. High levels of circulating Triggering Receptor Expressed on Myeloid cells-1 (TREM-1), were associated with death in acute myocardial infarction confirming excessive inflammation as determinant of bad outcome. The present study aims to describe the association of soluble TREM-1 with 90-day mortality and with various organ injuries in patients with CS. Methods and results This is a post-hoc study of CardShock, a prospective, multicenter study assessing the clinical presentation and management in patients with CS. At the time of this study, 87 patients had available plasma samples at either baseline, and/or 48 h and/or 96-120 h for soluble TREM-1 (sTREM-1) measurements. Plasma concentration of sTREM-1 was higher in 90-day non-survivors than survivors at baseline [median: 1392 IQR: (724-2128) vs. 621 (525-1233) pg/mL, p = 0.008), 48 h (p = 0.019) and 96-120 h (p = 0.029). The highest tertile of sTREM-1 at baseline (threshold: 1347 pg/mL) was associated with 90-day mortality with an unadjusted HR 3.08 CI 95% (1.48-6.42). sTREM-1 at baseline was not associated to hemodynamic parameters (heart rate, blood pressure, use of vasopressors or inotropes) but rather with organ injury markers: renal (estimated glomerular filtration rate, p = 0.0002), endothelial (bio-adrenomedullin, p = 0.018), myocardial (Suppression of Tumourigenicity 2, p = 0.002) or hepatic (bilirubin, p = 0.008). Conclusion In CS patients TREM-1 pathway is highly activated and gives an early prediction of vital organ injuries and outcome. [GRAPHICS] .
Published: 2022

3. Club 35 Poster Session Thursday 6 December: Intracardiac flows and pressures

Author: Jalanko, M, Jaaskelainen, P, Laine, M, Nieminen, MS, Laakso, M, Helio, T, and Kuusisto, J
Published: 2012

4. Effects of atorvastatin (and blood pressure lowering comparing amlodipide-based therapy with beta-blocker-based therapy) on serum variables of cholesterol synthesis and absorption, thrombogenicity and on low-density lipoprotein oxidation in vivo

Author: Nieminen, MS, Viikari, J, Ahotupa, M, Vasankari, T, Kantola, I, Strandberg, T, and Vanhanen, H
Published: 2001
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5. Comparative effects of atenolol-based and amlodipine-based antihypertensive therapy on QT dispersion in hypertensive subjects

Author: Oikarinen, L, Viitasalo, M, Toivonen, L, and Nieminen, MS
Published: 2001
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6. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery

Author: Szarek, M, Bhatt, DL, Bittner, VA, Diaz, R, Edelberg, JM, Hanotin, C, Harrington, RA, Jukema, JW, Letierce, A, Moryusef, A, Pordy, R, Lopez, GAR, Roe, MT, White, HD, Zeiher, AM, Steg, PG, Schwartz, GG, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, SH, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Alings, M, Halvorsen, S, Flores, RMC, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, de Silva, HA, Muller, C, Ray, KK, Vogel, R, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, van Diepen, SFP, Wilson, MD, Yan, ATK, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Rodolfo, AAG, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Lopes, RD, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Gotcheva, NN, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Chen, JY, Dong, YG, Huang, WJ, Wang, JZ, Huang, SA, Yao, ZH, Cui, L, Lin, WH, Sun, YM, Wang, JF, Li, JP, Zhang, XL, Zhu, H, Chen, DD, Huang, L, Dong, SH, Su, GH, Xu, B, Su, X, Cheng, XS, Lin, JX, Zong, WX, Li, HM, Feng, Y, Xu, DL, Yang, XC, Ke, YN, Lin, XF, Zhang, Z, Zheng, ZQ, Luo, ZR, Chen, YD, Ding, CH, Zheng, Y, Li, XD, Peng, DQ, Li, Y, Wei, M, Liu, SW, Yu, YH, Qu, BM, Jiang, WH, Zhou, YJ, Zhao, XS, Yuan, ZY, Guo, Y, Xu, XP, Shi, XB, Ge, JB, Fu, GS, Bai, F, Fang, WY, Shou, XL, Yang, XJ, Wang, JA, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Fernandez, AM, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Taskinen, MR, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Krohnert, U, Stratmann, M, Appel, KF, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Marx, N, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Liberopoulos, E, Skoumas, I, Athyros, V, Parthenakis, PIF, Hahalis, PIG, Lekakis, J, Xatzitolios, A, Ovando, SRF, Valdovinos, PCM, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Kiss, RG, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Palimkar, P, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Fujimoto, K, Yoon, JH, Park, HS, Chae, IH, Kim, MH, Jeong, MH, Rha, S, Kim, C, Hong, T, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Liew, HB, Mohamed, WMIW, Castillo, AG, Calvillo, JC, Campos, PF, Fragoso, JCN, Llamas, EAB, Gamba, MAA, Madrigal, JC, Salas, LGG, Rosas, EL, Diaz, BG, Vazquez, ES, Ackar, AN, Esperon, GAL, Sanchez, CRM, De Leon, MG, Otero, RS, Salmon, GF, Rios, JAP, Ruiz, JAG, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BRG, Troquay, RPT, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Hurtig, U, Ticona, JRC, Velasquez, JRD, Miguel, SAN, Perez, ESS, Chambilla, JMC, Ayala, CAC, Leon, RPC, Gonzales, RJV, Zuniga, JDH, Cosavalente, LAC, Mannucci, JEB, Navarro, NCL, Concha, YMR, Chavez, VER, Hernandez, HAA, Nunez, CAZ, Ferrolino, A, Sy, RAG, Tirador, L, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewoda, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminski, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Zuran, I, Oklukar, J, Suligoj, NC, Cevc, M, Lipar, L, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Dalby, AJ, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Hagstrom, E, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Torstensson, I, Jensen, SA, Ahremark, U, Sundelin, T, Moccetti, T, Mach, F, Binder, R, Chiang, CE, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Sritara, P, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Camsari, A, Kultursay, H, Guneri, S, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Parkhomenko, A, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SMR, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Moriarty, PM, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Schifferdecker, B, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, İÜC, and Ege Üniversitesi
Subjects: Male, medicine.medical_specialty, Acute coronary syndrome, alirocumab, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, lipids, PCSK9, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Double-Blind Method, coronary artery bypass graft, Internal medicine, medicine, Humans, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Acute Coronary Syndrome, Coronary Artery Bypass, Alirocumab, Aged, Kardiologi, business.industry, Unstable angina, Hazard ratio, cholesterol, Middle Aged, medicine.disease, surgical procedures, operative, Bypass surgery, Cardiovascular Diseases, Cardiology, Drug Therapy, Combination, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Mace
Abstract: Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.
Published: 2019
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7. Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Author: Steg, PG, Szarek, M, Bhatt, DL, Bittner, VA, Bregeault, M-F, Dalby, AJ, Diaz, R, Edelberg, JM, Goodman, SG, Hanotin, C, Harrington, RA, Jukema, JW, Lecorps, G, Mahaffey, KW, Moryusef, A, Ostadal, P, Parkhomenko, A, Pordy, R, Roe, MT, Tricoci, P, Vogel, R, White, HD, Zeiher, AM, Schwartz, GG, Sasiela, WJ, Tamby, J-F, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, NN, Prieto, J-C, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Marx, N, Liberopoulos, E, Valdovinos, PCM, Tse, H-F, Kiss, RG, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, S-H, Kedev, S, Erglis, A, Laucevicius, A, Yusoff, K, Lopez, R, Ramos Lopez, GA, Alings, M, Halvorsen, S, Correa Flores, RM, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, De Silva, HA, Hagstrom, E, Muller, C, Chiang, C-E, Sritara, P, Guneri, S, Ray, KK, Moriarty, PM, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, J-L, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Van Diepen, SFP, Wilson, MD, Yan, AT-K, Lopes, RD, Trotter, C, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, Alves De Lima, AE, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Angel Hominal, M, Montana, OR, Caccavo, A, Gomez Vilamajo, OA, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, R, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Ahuad Guerrero, RA, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Medrano Allende, JC, Garcia Brasca, DF, Bustamante Labarta, MH, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Zapata, G, Costamagna, O, Llois, S, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Oqueli Flores, RE, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Aroney, C, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Dick, R, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Goronja, B, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel Filho, P, Soggia, AP, De Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Fernandes Manenti, ERF, Precoma, DB, Moura Jorge, JC, Silva, PGMDB, Silveira, JA, Saporito, W, Marin Neto, JA, Feitosa, GS, Ritt, LEF, De Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Machado, L, Aidar Ayoub, JC, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, 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Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, HT, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, C, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm, İÜC, Ege Üniversitesi, Rushton-Smith, Sophie, and ODYSSEY OUTCOMES Committees and Investigators
Subjects: Male, Cardiac & Cardiovascular Systems, MONOCLONAL-ANTIBODY, alirocumab, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, law.invention, PCSK9, chemistry.chemical_compound, Randomized controlled trial, law, Cardiac and Cardiovascular Systems, 1102 Cardiorespiratory Medicine and Haematology, Hypercholesterolemia/blood, Kardiologi, Hazard ratio, Middle Aged, Treatment Outcome, SAFETY, Cardiology, Female, Drug Therapy, Combination, Cholesterol, LDL/antagonists & inhibitors, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, REDUCING LIPIDS, Akutes Koronarsyndrom, acute coronary syndrome, cholesterol, mortality, PCSK9 protein, Antibodies, Monoclonal, Humanized/administration & dosage, medicine.medical_specialty, Acute coronary syndrome, Injections, Subcutaneous, Hypercholesterolemia, Placebo, Antibodies, Monoclonal, Humanized, 1117 Public Health and Health Services, Sterblichkeit, Double-Blind Method, Physiology (medical), Internal medicine, medicine, Humans, ddc:610, Alirocumab, Aged, Science & Technology, Cholesterol, business.industry, EVOLOCUMAB, 1103 Clinical Sciences, Cholesterol, LDL, medicine.disease, EFFICACY, Increased risk, chemistry, Peripheral Vascular Disease, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, Acute Coronary Syndrome/blood, Cholesterin, Human medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Follow-Up Studies
Abstract: bastos, jose/0000-0002-9526-3123; Manakshe, Gajendra/0000-0002-4983-4271; Tse, Hung Fat/0000-0002-9578-7808; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Racca, Vittorio/0000-0002-4465-3789; Keskin, Kudret/0000-0002-9049-1530; Sherwood, Matthew/0000-0002-4305-5883; Sandhu, Manjinder/0000-0003-2538-2079; Nikolaev, Konstantin/0000-0003-4601-6203; Ersanli, Murat/0000-0003-1847-3087; Raffel, Owen C/0000-0001-5470-7050; Abbate, Antonio/0000-0002-1930-785X; Muenzel, Thomas/0000-0001-5503-4150; Leonardi, Sergio/0000-0002-4800-6132; Chumakova, Galina A/0000-0002-2810-6531; Podoleanu, Cristian/0000-0001-9987-2519; Pereira, Helder/0000-0001-8656-4883; Reshetko, Olga/0000-0003-3107-7636, WOS: 000476768100007, PubMed: 31117810, Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. in a prespecified analysis of 8242 patients eligible for >= 3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P= 100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P-interaction=0.007). in the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >= 3 years, if baseline LDL-C is >= 100 mg/dL, or if achieved LDL-C is low., Sanofi; Regeneron Pharmaceuticals, Inc., The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.
Published: 2019
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8. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial

Author: DiCenso, D, Gotcheva, N, Sourdille, T, White, HD, Schwartz, GG, Steg, PG, Bhatt, DL, Bittner, VA, Diaz, R, Harrington, RA, Jukema, JW, Szarek, M, Zeiher, AM, Tricoci, P, Mahaffey, KW, Edelberg, JM, Hanotin, C, Lecorps, G, Moryusef, A, Pordy, R, Sasiela, WJ, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, NN, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kim, HS, Erglis, A, Laucevicius, A, Lopez, R, Lopez, GAR, Alings, M, Chua, T, Murin, J, Fras, Z, Dalby, AJ, Tunon, J, De Silva, HA, Chiang, CE, Sritara, P, Guneri, S, Parkhomenko, A, Ray, KK, Moriarty, PM, Roe, MT, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Van Diepen, SFP, Wilson, MD, Yan, ATK, Lopes, RD, Trotter, C, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, R, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Guerrero, RAA, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Zapata, G, Costamagna, O, Llois, S, Waites, JH, Collins, N, Soward, A, Aylward, PE, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Aroney, C, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Dick, R, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Goronja, B, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, Saporito, W, Marin, JA, Feitosa, GS, Ritt, LEF, de Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Machado, L, Ayoub, JCA, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Nahuelpan, L, Montecinos, H, Chen, JY, Dong, YG, Huang, WJ, Wang, JZ, Huang, SA, Yao, ZH, Li, X, Cui, L, Lin, WH, Sun, YM, Wang, JF, Li, JP, Zhang, XL, Zhu, H, Chen, D, Huang, L, Dong, SH, Su, GH, Xu, BA, Su, X, Cheng, XS, Lin, JX, Zong, WX, Li, HM, Feng, Y, Xu, DL, Yang, XC, Ke, YN, Lin, XF, Zhang, Z, Zheng, ZQ, Luo, ZR, Chen, YD, Ding, CH, Zheng, Y, Li, XD, Peng, DQ, Li, Y, Wei, M, Liu, SW, Yu, YH, Qu, BM, Jiang, WH, Zhou, YJ, Zhao, XS, Yuan, ZY, Guo, Y, Xu, XP, Shi, XB, Ge, JB, Fu, GS, Bai, F, Fang, WY, Shou, XL, Yang, XJ, Wang, JA, Sun, YX, Lu, QH, Zhang, RY, Zhu, JH, Xu, YZ, Fan, ZC, Li, TC, Wu, C, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Strozzi, M, Car, S, Milicic, D, Bencic, ML, Pintaric, H, Prvulovic, D, Sikic, J, Persic, V, Mileta, D, Stambuk, K, Zdravko, B, Tomulic, V, Krstulovic, SM, Starcevic, B, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Ostadal, P, Heinc, P, Kuchar, J, Povolny, P, Matuska, J, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Kristjan, A, Taskinen, MR, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Citron, B, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Krohnert, U, Stratmann, M, Appel, KF, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Marx, N, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Bocker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voller, H, Waltenberger, J, Natour, M, Schmitt, S, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Rieker, W, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Liberopoulos, E, Skoumas, I, Athyros, V, Vardas, P, Parthenakis, F, Alexopoulos, D, Hahalis, G, Lekakis, J, Hatzitolios, A, Ovando, SRF, Valdovinos, PCM, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Kiss, RG, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Abdullkutty, J, Sathe, S, Palimkar, P, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Lishner, M, Elias, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Ricca, V, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Kimura, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Masutani, M, Fujimoto, K, Yoon, JH, Kim, SH, Park, HS, Chae, IH, Kim, MH, Jeong, MH, Rha, S, Kim, C, Hong, T, Tahk, SJ, Kim, Y, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Kedev, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Yusoff, K, Liew, HB, Mohamed, WMIW, Castillo, AG, Calvillo, JC, Campos, PF, Fragoso, JCN, Llamas, EAB, Gamba, MAA, Madrigal, JC, Salas, LGG, Rosas, EL, Diaz, BG, Vazquez, ES, Ackar, AN, Esperon, GAL, Sanchez, CRM, De Leon, MG, Otero, RS, Salmon, GF, Rios, JA, Ruiz, JAG, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BR, Troquay, RPT, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Davidson, L, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Singsaas, EG, Halvorsen, S, Hurtig, U, Flores, RMC, Ticona, JRC, Velasquez, JRD, Miguel, SAN, Perez, ESS, Chambilla, JMC, Ayala, CAC, Leon, RPC, Gonzales, RJV, Zuniga, JDH, Cosavalente, LAC, Mannucci, JEB, Landeo, JH, Navarro, NCL, Concha, YMR, Chavez, VER, Hernandez, HAA, Nunez, CAZ, Ramos, WM, Ferrolino, A, Sy, RAG, Tirador, L, Sy, RG, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Sulit, DJ, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewod, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Budaj, A, Saminsk, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Raczak, G, Szwed, H, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Morais, J, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Dorobantu, M, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Coman, I, Cioranu, RS, Dimulescu, D, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Karpov, Y, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Kanorsky, S, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Ristic, AD, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, KK, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Olexa, P, Zuran, I, Poklukar, J, Suligoj, NC, Cevc, M, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMD, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Reuter, H, Moodley, R, Vida, M, Fillat, ARC, Peris, VB, Jimenez, FF, Marin, F, Fernandez, JMC, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Fernandez, JT, Gonzalez-Juanatey, JR, Portales, JF, Murillo, FC, Pericas, LM, Zamorano, JL, Martin, MD, Cortada, JB, Martin, JJA, Fernandez, JRD, Fernandez, JFD, Lledo, JAG, Sales, JC, Rodriguez, JB, Tragant, GG, Benedicto, A, Gonzalez-Juanatey, C, Potau, MC, Perez, IP, De La Tassa, CM, Rincon, PLO, Recena, JB, Escudier, JM, Payeras, AC, Orcajo, NA, Valdivielso, P, Constantine, G, Haniffa, R, Tissera, N, Amarasekera, S, Fernando, N, Jayawardena, J, Santharaj, W, Ekanayaka, R, Mendis, S, Senaratne, V, Mayurathan, G, Sirisena, T, Rajapaksha, A, Herath, JI, Amarasena, N, Berglund, S, Rasmanis, G, Witt, N, Mourtzinis, G, Nicol, P, Hansen, O, Romeo, S, Jensen, SA, Torstensson, I, Ahremark, U, Sundelin, T, Moccetti, T, Muller, C, Mach, F, Binder, R, Tsai, WC, Ueng, KC, Lai, WT, Liu, ME, Hwang, JJ, Yin, WH, Hsieh, IC, Kuo, JY, Huang, TY, Fang, CY, Kaewsuwanna, P, Soonfuang, W, Jintapakorn, W, Sukonthasarn, A, Wongpraparut, N, Sastravaha, K, Sansanayudh, N, Kehasukcharoen, W, Piyayotai, D, Chotnoparatpat, P, Camsari, A, Kultursay, H, Mutlu, B, Ersanli, M, Demirtas, M, Kirma, C, Ural, E, Koldas, L, Karpenko, O, Prokhorov, A, Vakaluyk, I, Myshanych, H, Reshotko, D, Batushkin, V, Rudenko, L, Kovalskyi, I, Kushnir, M, Tseluyko, V, Mostovoy, Y, Stanislavchuk, M, Kyiak, Y, Karpenko, Y, Malynovsky, Y, Klantsa, A, Kutniy, O, Amosova, E, Tashchuk, V, Leshchuk, O, Rishko, M, Kopytsya, M, Yagensky, A, Vatutin, M, Bagriy, A, Barna, OM, Ushakov, O, Dzyak, G, Goloborodko, B, Rudenko, A, Zheleznyy, V, Trevelyan, J, Zaman, A, Lee, K, Moriarty, A, Aggarwal, RK, Clifford, P, Wong, YK, Iqbal, SM, Subkovas, E, Braganza, D, Sarkar, D, Storey, R, Griffiths, H, Mcclure, S, Muthusamy, R, Kurian, J, Levy, T, Barr, C, Kadr, H, Gerber, R, Simaitis, A, Soran, H, Mathur, A, Brodison, A, Oliver, R, Mudawi, T, Reynolds, T, Sharman, D, Butler, R, Wilkinson, P, Lip, GYH, Halcox, J, Vardi, G, Baldari, D, Brabham, D, Treasure, C, Dahl, C, Palmer, B, Wiseman, A, Puri, S, Mohart, AE, Ince, C, Flores, E, Wright, S, Cheng, SC, Rosenberg, M, Rogers, W, Kosinski, E, Forgosh, L, Waltman, J, Khan, M, Shoukfeh, M, Dagher, G, Lieber, I, Kumar, P, East, C, Krichmar, P, White, L, Knickelbine, T, Haldis, T, Gillespie, E, Suh, D, Arif, I, Akhter, F, Carlson, E, D'Urso, M, El-Ahdab, F, Nelson, W, Harris, B, Cohen, S, Carter, L, Sabatino, K, Haddad, T, Malik, A, Rao, S, Mulkay, A, Jovin, I, Klancke, K, Malhotra, V, Devarapalli, SK, Koren, M, Chandna, H, Dodds, G, Janik, M, Moran, J, Sumner, A, Kobayashi, J, Davis, W, Yazdani, S, Pasquini, J, Thakkar, M, Vedere, A, Leimbach, W, Rider, J, Singh, N, Shah, AV, Janosik, D, Pepine, C, Berman, B, Gelormini, J, Daniels, C, Keating, F, Kondo, NI, Shetty, S, Waider, W, Takata, T, Abu-Fadel, M, Shah, V, Aggarwal, R, Izzo, M, Kumar, A, Hattler, B, Link, C, Bortnick, A, Kinzfogl, G, Ghitis, A, Larry, J, Teufel, E, Kuhlman, P, Mclaurin, B, Zhang, WW, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Hagstrom, E, Grunberg, L, Islam, S, Bregeault, MF, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Tamby, JF, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, CY, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm Inve, Ege Üniversitesi, Cardiology, and Internal Medicine
Subjects: medicine.medical_specialty, Acute coronary syndrome, Time Factors, acute coronary syndrome, alirocumab, global burden of disease, hospitalization, myocardial infarction, PCSK9, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Placebo, Patient Readmission, Risk Assessment, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Angina, Unstable, Hospital Mortality, 030212 general & internal medicine, Myocardial infarction, 03.02. Klinikai orvostan, Dyslipidemias, Alirocumab, Out of hospital, business.industry, Anticholesteremic Agents, Cholesterol, HDL, Cholesterol hdl, Cholesterol, LDL, medicine.disease, Treatment Outcome, Drug Therapy, Combination, Human medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Cardiovascular outcomes, Biomarkers
Abstract: Sherwood, Matthew/0000-0002-4305-5883; Abbate, Antonio/0000-0002-1930-785X; Moris, Cesar/0000-0002-2871-190X; Ersanli, Murat/0000-0003-1847-3087; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Reshetko, Olga/0000-0003-3107-7636; Nikolaev, Konstantin/0000-0003-4601-6203; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Gislason, Gunnar H/0000-0002-0548-402X; Muenzel, Thomas/0000-0001-5503-4150; Tse, Hung Fat/0000-0002-9578-7808; Chumakova, Galina A/0000-0002-2810-6531, WOS: 000502609000004, PubMed: 31707826, Background: in ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. the present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: in prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03). Conclusions: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, We thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the article (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.
Published: 2019
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9. Quality control and conduct of genome-wide association meta-analyses

Author: Winkler, T, Day, F, Croteau Chonka, D, Wood, A, Locke, A, Mägi, R, Ferreira, T, Fall, T, Graff, M, Justice, A, Luan, J, Gustafsson, S, Randall, J, Vedantam, S, Workalemahu, T, Kilpeläinen, T, Scherag, A, Esko, T, Kutalik, Z, Heid, I, Loos, R, Abecasis GR, Absher D, Alavere H, Albrecht E, Allen HL, Almgren P, Amin N, Amouyel P, Anderson D, Arnold AM, Arveiler D, Aspelund T, Asselbergs FW, Assimes TL, Atalay M, Attwood AP, Atwood LD, Bakker SJ, Balkau B, Balmforth AJ, Barlassina C, Barroso I, Basart H, Bauer S, Beckmann JS, Beilby JP, Bennett AJ, Ben Shlomo Y, Bergman RN, Bergmann S, Berndt SI, Biffar R, Di Blasio AM, Boehm BO, Boehnke M, Boeing H, Boerwinkle E, Bolton JL, Bonnefond A, Bonnycastle LL, Boomsma DI, Borecki IB, Bornstein SR, Bouatia Naji N, Boucher G, Bragg Gresham JL, BRAMBILLA, PAOLO, Bruinenberg M, Buchanan TA, Buechler C, Cadby G, Campbell H, Caulfield MJ, Cavalcanti Proença C, CESANA, GIANCARLO, Chanock SJ, Chasman DI, Chen YD, Chines PS, Clegg DJ, Coin L, Collins FS, Connell JM, Cookson W, Cooper MN, Croteau Chonka DC, Cupples LA, Cusi D, Day FR, Day IN, Dedoussis GV, Dei M, Deloukas P, Dermitzakis ET, Dimas AS, Dimitriou M, Dixon AL, Dörr M, van Duijn CM, Ebrahim S, Edkins S, Eiriksdottir G, Eisinger K, Eklund N, Elliott P, Erbel R, Erdmann J, Erdos MR, Eriksson JG, Esko T, Estrada K, Evans DM, de Faire U, Fall T, Farrall M, Feitosa MF, Ferrario MM, Ferreira T, Ferrières J, Fischer K, Fisher E, Fowkes G, Fox CS, Franke L, Franks PW, Fraser RM, Frau F, Frayling T, Freimer NB, Froguel P, Fu M, Gaget S, Ganna A, Gejman PV, Gentilini D, Geus EJ, Gieger C, Gigante B, Gjesing AP, Glazer NL, Goddard ME, Goel A, Grallert H, Gräßler J, Grönberg H, Groop LC, Groves CJ, Gudnason V, Guiducci C, Gustafsson S, Gyllensten U, Hall AS, Hall P, Hallmans G, Hamsten A, Hansen T, Haritunians T, Harris TB, van der Harst P, Hartikainen AL, Hassanali N, Hattersley AT, Havulinna AS, Hayward C, Heard Costa NL, Heath AC, Hebebrand J, Heid IM, den Heijer M, Hengstenberg C, Herzig KH, Hicks AA, Hingorani A, Hinney A, Hirschhorn JN, Hofman A, Holmes CC, Homuth G, Hottenga JJ, Hovingh KG, Hu FB, Hu YJ, Huffman JE, Hui J, Huikuri H, Humphries SE, Hung J, Hunt SE, Hunter D, Hveem K, Hyppönen E, Igl W, Illig T, Ingelsson E, Iribarren C, Isomaa B, Jackson AU, Jacobs KB, James AL, Jansson JO, Jarick I, Jarvelin MR, Jöckel KH, Johansson Å, Johnson T, Jolley J, Jørgensen T, Jousilahti P, Jula A, Justice AE, Kaakinen M, Kähönen M, Kajantie E, Kanoni S, Kao WH, Kaplan LM, Kaplan RC, Kaprio J, Kapur K, Karpe F, Kathiresan S, Kee F, Keinanen Kiukaanniemi SM, Ketkar S, Kettunen J, Khaw KT, Kiemeney LA, Kilpeläinen TO, Kinnunen L, Kivimaki M, Kivmaki M, Van der Klauw MM, Kleber ME, Knowles JW, Koenig W, Kolcic I, Kolovou G, König IR, Koskinen S, Kovacs P, Kraft P, Kraja AT, Kristiansson K, KrjutÅjkov K, Kroemer HK, Krohn JP, Krzelj V, Kuh D, Kulzer JR, Kumari M, Kutalik Z, Kuulasmaa K, Kuusisto J, Kvaloy K, Laakso M, Laitinen JH, Lakka TA, Lamina C, Langenberg C, Lantieri O, Lathrop GM, Launer LJ, Lawlor DA, Lawrence RW, Leach IM, Lecoeur C, Lee SH, Lehtimäki T, Leitzmann MF, Lettre G, Levinson DF, Li G, Li S, Liang L, Lin DY, Lind L, Lindgren CM, Lindström J, Liu J, Liuzzi A, Locke AE, Lokki ML, Loley C, Loos RJ, Lorentzon M, Luan J, Luben RN, Ludwig B, Madden PA, Mägi R, Magnusson PK, Mangino M, Manunta P, Marek D, Marre M, Martin NG, März W, Maschio A, Mathieson I, McArdle WL, McCaroll SA, McCarthy A, McCarthy MI, McKnight B, Medina Gomez C, Medland SE, Meitinger T, Metspalu A, van Meurs JB, Meyre D, Midthjell K, Mihailov E, Milani L, Min JL, Moebus S, Moffatt MF, Mohlke KL, Molony C, Monda KL, Montgomery GW, Mooser V, Morken MA, Morris AD, Morris AP, Mühleisen TW, Müller Nurasyid M, Munroe PB, Musk AW, Narisu N, Navis G, Neale BM, Nelis M, Nemesh J, Neville MJ, Ngwa JS, Nicholson G, Nieminen MS, Njølstad I, Nohr EA, Nolte IM, North KE, Nöthen MM, Nyholt DR, O'Connell JR, Ohlsson C, Oldehinkel AJ, van Ommen GJ, Ong KK, Oostra 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Stančáková A, Stark K, Stefansson K, Steinthorsdottir V, Stephens JC, Stirrups K, Stolk RP, Strachan DP, Strawbridge RJ, Stringham HM, Stumvoll M, Surakka I, Swift AJ, Syvanen AC, Tammesoo ML, Teder Laving M, Teslovich TM, Teumer A, Theodoraki EV, Thomson B, Thorand B, Thorleifsson G, Thorsteinsdottir U, Timpson NJ, Tönjes A, Tregouet DA, Tremoli E, Trip MD, Tuomi T, Tuomilehto J, Tyrer J, Uda M, Uitterlinden AG, Usala G, Uusitupa M, Valle TT, Vandenput L, Vatin V, Vedantam S, de Vegt F, Vermeulen SH, Viikari J, Virtamo J, Visscher PM, Vitart V, Van Vliet Ostaptchouk JV, Voight BF, Vollenweider P, Volpato CB, Völzke H, Waeber G, Waite LL, Wallaschofski H, Walters GB, Wang Z, Wareham NJ, Watanabe RM, Watkins H, Weedon MN, Welch R, Weyant RJ, Wheeler E, White CC, Wichmann HE, Widen E, Wild SH, Willemsen G, Willer CJ, Wilsgaard T, Wilson JF, van Wingerden S, Winkelmann BR, Winkler TW, Witte DR, Witteman JC, Wolffenbuttel BH, Wong A, Wood AR, Workalemahu T, Wright AF, Yang J, Yarnell JW, 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Nicholson, G, Nieminen, M, Njølstad, I, Nohr, E, Nolte, I, North, K, Nöthen, M, Nyholt, D, O'Connell, J, Ohlsson, C, Oldehinkel, A, van Ommen, G, Ong, K, Oostra, B, Ouwehand, W, Palmer, C, Palmer, L, Palotie, A, Paré, G, Parker, A, Paternoster, L, Pawitan, Y, Pechlivanis, S, Peden, J, Pedersen, N, Pedersen, O, Pellikka, N, Peltonen, L, Penninx, B, Perola, M, Perry, J, Person, T, Peters, A, Peters, M, Pichler, I, Pietiläinen, K, Platou, C, Polasek, O, Pouta, A, Power, C, Pramstaller, P, Preuss, M, Price, J, Prokopenko, I, Province, M, Psaty, B, Purcell, S, Pütter, C, Qi, L, Quertermous, T, Radhakrishnan, A, Raitakari, O, Rauramaa, R, Rayner, N, Rehnberg, E, Rendon, A, Ridderstråle, M, Ridker, P, Ripatti, S, Rissanen, A, Rivadeneira, F, Rivolta, C, Robertson, N, Rose, L, Rudan, I, Saaristo, T, Sager, H, Salomaa, V, Samani, N, Sambrook, J, Sanders, A, Sandholt, C, Sanna, S, Saramies, J, Schadt, E, Schipf, S, Schlessinger, D, Schreiber, S, Schunkert, H, Schwarz, P, Scott, L, Shi, J, Shin, S, Shuldiner, A, Shungin, D, Signorini, S, Silander, K, Sinisalo, J, Skrobek, B, Smit, J, Smith, A, Smith, G, Snieder, H, Soranzo, N, Sørensen, T, Sovio, U, Spector, T, Speliotes, E, Stančáková, A, Stark, K, Stefansson, K, Steinthorsdottir, V, Stephens, J, Stirrups, K, Stolk, R, Strachan, D, Strawbridge, R, Stringham, H, Stumvoll, M, Surakka, I, Swift, A, Syvanen, A, Tammesoo, M, Teder Laving, M, Teslovich, T, Teumer, A, Theodoraki, E, Thomson, B, Thorand, B, Thorleifsson, G, Thorsteinsdottir, U, Timpson, N, Tönjes, A, Tregouet, D, Tremoli, E, Trip, M, Tuomi, T, Tuomilehto, J, Tyrer, J, Uda, M, Uitterlinden, A, Usala, G, Uusitupa, M, Valle, T, Vandenput, L, Vatin, V, de Vegt, F, Vermeulen, S, Viikari, J, Virtamo, J, Visscher, P, Vitart, V, Van Vliet Ostaptchouk, J, Voight, B, Vollenweider, P, Volpato, C, Völzke, H, Waeber, G, Waite, L, Wallaschofski, H, Walters, G, Wang, Z, Wareham, N, Watanabe, R, Watkins, H, Weedon, M, Welch, R, Weyant, R, Wheeler, E, White, C, Wichmann, H, Widen, E, Wild, S, Willemsen, G, Willer, C, Wilsgaard, T, Wilson, J, van Wingerden, S, Winkelmann, B, Witte, D, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Yang, J, Yarnell, J, Zgaga, L, Zhao, J, Zillikens, M, Zitting, P, Zondervan, K, Psychiatry, EMGO - Mental health, Plastic, Reconstructive and Hand Surgery, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Cardiology, Biological Psychology, EMGO+ - Mental Health, Genetic Investigation of Anthropometric Traits (GIANT) Consortium, Abecasis, GR., Absher, D., Alavere, H., Albrecht, E., Allen, HL., Almgren, P., Amin, N., Amouyel, P., Anderson, D., Arnold, AM., Arveiler, D., Aspelund, T., Asselbergs, FW., Assimes, TL., Atalay, M., Attwood, AP., Atwood, LD., Bakker, SJ., Balkau, B., Balmforth, AJ., Barlassina, C., Barroso£££Inês£££ I., Basart, H., Bauer, S., Beckmann, JS., Beilby, JP., Bennett, AJ., Ben-Shlomo, Y., Bergman, RN., Bergmann, S., Berndt, SI., Biffar, R., Di Blasio AM., Boehm, BO., Boehnke, M., Boeing, H., Boerwinkle, E., Bolton, JL., Bonnefond, A., Bonnycastle, LL., Boomsma, DI., Borecki, IB., Bornstein, SR., Bouatia-Naji, N., Boucher, G., Bragg-Gresham, JL., Brambilla, P., Bruinenberg, M., Buchanan, TA., Buechler, C., Cadby, G., Campbell, H., Caulfield, MJ., Cavalcanti-Proença, C., Cesana, G., Chanock, SJ., Chasman, DI., Chen, YD., Chines, PS., Clegg, DJ., Coin, L., Collins, FS., Connell, JM., Cookson, W., Cooper, MN., Croteau-Chonka, DC., Cupples, LA., Cusi, D., Day, FR., Day, IN., Dedoussis, GV., Dei, M., Deloukas, P., Dermitzakis, ET., Dimas, AS., Dimitriou, M., Dixon, AL., Dörr, M., van Duijn CM., Ebrahim, S., Edkins, S., Eiriksdottir, G., Eisinger, K., Eklund, N., Elliott, P., Erbel, R., Erdmann, J., Erdos, MR., Eriksson, JG., Esko£££Tõnu£££ T., Estrada, K., Evans, DM., de Faire, U., Fall, T., Farrall, M., Feitosa, MF., Ferrario, MM., Ferreira, T., Ferrières, J., Fischer, K., Fisher, E., Fowkes, G., Fox, CS., Franke, L., Franks, PW., Fraser, RM., Frau, F., Frayling, T., Freimer, NB., Froguel, P., Fu, M., Gaget, S., Ganna, A., Gejman, PV., Gentilini, D., Geus, EJ., Gieger, C., Gigante, B., Gjesing, AP., Glazer, NL., Goddard, ME., Goel, A., Grallert, H., Gräßler, J., Grönberg, H., Groop, LC., Groves, CJ., Gudnason, V., Guiducci, C., Gustafsson, S., Gyllensten, U., Hall, AS., Hall, P., Hallmans, G., Hamsten, A., Hansen, T., Haritunians, T., Harris, TB., van der Harst, P., Hartikainen, AL., Hassanali, N., Hattersley, AT., Havulinna, AS., Hayward, C., Heard-Costa, NL., Heath, AC., Hebebrand, J., Heid, IM., den Heijer, M., Hengstenberg, C., Herzig, KH., Hicks, AA., Hingorani, A., Hinney, A., Hirschhorn, JN., Hofman, A., Holmes, CC., Homuth, G., Hottenga, JJ., Hovingh, KG., Hu, FB., Hu, YJ., Huffman, JE., Hui, J., Huikuri, H., Humphries, SE., Hung, J., Hunt, SE., Hunter, D., Hveem, K., Hyppönen, E., Igl, W., Illig, T., Ingelsson, E., Iribarren, C., Isomaa, B., Jackson, AU., Jacobs, KB., James, AL., Jansson, JO., Jarick, I., Jarvelin, MR., Jöckel, KH., Johansson£££Åsa£££ Å., Johnson, T., Jolley, J., Jørgensen, T., Jousilahti, P., Jula, A., Justice, AE., Kaakinen, M., Kähönen, M., Kajantie, E., Kanoni, S., Kao, WH., Kaplan, LM., Kaplan, RC., Kaprio, J., Kapur, K., Karpe, F., Kathiresan, S., Kee, F., Keinanen-Kiukaanniemi, SM., Ketkar, S., Kettunen, J., Khaw, KT., Kiemeney, LA., Kilpeläinen, TO., Kinnunen, L., Kivimaki, M., Kivmaki, M., Van der Klauw MM., Kleber, ME., Knowles, JW., Koenig, W., Kolcic, I., Kolovou, G., König, IR., Koskinen, S., Kovacs, P., Kraft, P., Kraja, AT., Kristiansson, K., KrjutÅjkov, K., Kroemer, HK., Krohn, JP., Krzelj, V., Kuh, D., Kulzer, JR., Kumari, M., Kutalik£££Zoltán£££ Z., Kuulasmaa, K., Kuusisto, J., Kvaloy, K., Laakso, M., Laitinen, JH., Lakka, TA., Lamina, C., Langenberg, C., Lantieri, O., Lathrop, GM., Launer, LJ., Lawlor, DA., Lawrence, RW., Leach, IM., Lecoeur, C., Lee, SH., Lehtimäki, T., Leitzmann, MF., Lettre, G., Levinson, DF., Li, G., Li, S., Liang, L., Lin, DY., Lind, L., Lindgren, CM., Lindström, J., Liu, J., Liuzzi, A., Locke, AE., Lokki, ML., Loley, C., Loos, RJ., Lorentzon, M., Luan£££Jian'an£££ J., Luben, RN., Ludwig, B., Madden, PA., Mägi, R., Magnusson, PK., Mangino, M., Manunta, P., Marek, D., Marre, M., Martin, NG., März, W., Maschio, A., Mathieson, I., McArdle, WL., McCaroll, SA., McCarthy, A., McCarthy, MI., McKnight, B., Medina-Gomez, C., Medland, SE., Meitinger, T., Metspalu, A., van Meurs JB., Meyre, D., Midthjell, K., Mihailov, E., Milani, L., Min, JL., Moebus, S., Moffatt, MF., Mohlke, KL., Molony, C., Monda, KL., Montgomery, GW., Mooser, V., Morken, MA., Morris, AD., Morris, AP., Mühleisen, TW., Müller-Nurasyid, M., Munroe, PB., Musk, AW., Narisu, N., Navis, G., Neale, BM., Nelis, M., Nemesh, J., Neville, MJ., Ngwa, JS., Nicholson, G., Nieminen, MS., Njølstad, I., Nohr, EA., Nolte, IM., North, KE., Nöthen, MM., Nyholt, DR., O'Connell, JR., Ohlsson, C., Oldehinkel, AJ., van Ommen GJ., Ong, KK., Oostra, BA., Ouwehand, WH., Palmer, CN., Palmer, LJ., Palotie, A., Paré, G., Parker, AN., Paternoster, L., Pawitan, Y., Pechlivanis, S., Peden, JF., Pedersen, NL., Pedersen, O., Pellikka, N., Peltonen, L., Penninx, B., Perola, M., Perry, JR., Person, T., Peters, A., Peters, MJ., Pichler, I., Pietiläinen, KH., Platou, CG., Polasek, O., Pouta, A., Power, C., Pramstaller, PP., Preuss, M., Price, JF., Prokopenko, I., Province, MA., Psaty, BM., Purcell, S., Pütter, C., Qi, L., Quertermous, T., Radhakrishnan, A., Raitakari, O., Randall, JC., Rauramaa, R., Rayner, NW., Rehnberg, E., Rendon, A., Ridderstråle, M., Ridker, PM., Ripatti, S., Rissanen, A., Rivadeneira, F., Rivolta, C., Robertson, NR., Rose, LM., Rudan, I., Saaristo, TE., Sager, H., Salomaa, V., Samani, NJ., Sambrook, JG., Sanders, AR., Sandholt, C., Sanna, S., Saramies, J., Schadt, EE., Scherag, A., Schipf, S., Schlessinger, D., Schreiber, S., Schunkert, H., Schwarz, PE., Scott, LJ., Shi, J., Shin, SY., Shuldiner, AR., Shungin, D., Signorini, S., Silander, K., Sinisalo, J., Skrobek, B., Smit, JH., Smith, AV., Smith, GD., Snieder, H., Soranzo, N., Sørensen, TI., Sovio, U., Spector, TD., Speliotes, EK., Stančáková, A., Stark, K., Stefansson, K., Steinthorsdottir, V., Stephens, JC., Stirrups, K., Stolk, RP., Strachan, DP., Strawbridge, RJ., Stringham, HM., Stumvoll, M., Surakka, I., Swift, AJ., Syvanen, AC., Tammesoo, ML., Teder-Laving, M., Teslovich, TM., Teumer, A., Theodoraki, EV., Thomson, B., Thorand, B., Thorleifsson, G., Thorsteinsdottir, U., Timpson, NJ., Tönjes, A., Tregouet, DA., Tremoli, E., Trip, MD., Tuomi, T., Tuomilehto, J., Tyrer, J., Uda, M., Uitterlinden, AG., Usala, G., Uusitupa, M., Valle, TT., Vandenput, L., Vatin, V., Vedantam, S., de Vegt, F., Vermeulen, SH., Viikari, J., Virtamo, J., Visscher, PM., Vitart, V., Van Vliet-Ostaptchouk JV., Voight, BF., Vollenweider, P., Volpato, CB., Völzke, H., Waeber, G., Waite, LL., Wallaschofski, H., Walters, GB., Wang, Z., Wareham, NJ., Watanabe, RM., Watkins, H., Weedon, MN., Welch, R., Weyant, RJ., Wheeler, E., White, CC., Wichmann, HE., Widen, E., Wild, SH., Willemsen, G., Willer, CJ., Wilsgaard, T., Wilson, JF., van Wingerden, S., Winkelmann, BR., Winkler, TW., Witte, DR., Witteman, JC., Wolffenbuttel, BH., Wong, A., Wood, AR., Workalemahu, T., Wright, AF., Yang, J., Yarnell, JW., Zgaga, L., Zhao, JH., Zillikens, MC., Zitting, P., and Zondervan, KT.
Subjects: Quality Control, Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, media_common.quotation_subject, quality control, GWAMAS, Control (management), Medizin, Genome-wide association study, Biology, Bioinformatics, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Software, SDG 17 - Partnerships for the Goals, Meta-Analysis as Topic, Comparable size, Quality (business), 030304 developmental biology, media_common, Protocol (science), 0303 health sciences, business.industry, Software package, Data science, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Genome-Wide Association Study/methods, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], quality control, genome-wide association meta-analyses, business, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Item does not contain fulltext Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta-level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.
Published: 2014
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10. Third universal definition of myocardial infarction

Author: Thygesen, K, Alpert, Js, Jaffe, As, Simoons, Ml, Chaitman, Br, White, Hd, the Writing Group on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Universal Definition of Myocardial Infarction, Authors/Task Force Members Chairpersons, Biomarker, Subcommittee, Katus, Ha, Apple, Fs, Lindahl, B, Morrow, Da, Ecg, Subcommittee, Clemmensen, Pm, Johanson, P, Hod, H, Imaging, Subcommittee, Underwood, R, Bax, Jj, Bonow, Ro, Pinto, F, Gibbons, Rj, Classification, Subcommittee, Fox, Ka, Atar, D, Newby, Lk, Galvani, M, Hamm, Cw, Intervention, Subcommittee, Uretsky, Bf, Gabriel Steg, P, Wijns, W, Bassand, Jp, Menasché, P, Ravkilde, J, Trials, Registries, Subcommittee, Ohman, Em, Antman, Em, Wallentin, Lc, Armstrong, Pw, Heart Failure Subcommittee, Januzzi, Jl, Nieminen, Ms, Gheorghiade, M, Filippatos, G, Epidemiology, Subcommittee, Luepker, Rv, Fortmann, Sp, Rosamond, Wd, Levy, D, Wood, D, Global Perspective Subcommittee, Smith, Sc, Hu, D, Lopez Sendon JL, Robertson, Rm, Weaver, D, Tendera, M, Bove, Aa, Parkhomenko, An, Vasilieva, Ej, Mendis, S, ESC Committee for Practice Guidelines, Baumgartner, H, Ceconi, Claudio, Dean, V, Deaton, C, Fagard, R, Funck Brentano, C, Hasdai, D, Hoes, A, Kirchhof, P, Knuuti, J, Kolh, P, Mcdonagh, T, Moulin, C, Popescu, Ba, Reiner, Z, Sechtem, U, Sirnes, Pa, Torbicki, A, Vahanian, A, Windecker, S, Document, Reviewers, Morais, J, Aguiar, C, Almahmeed, W, Arnar, Do, Barili, F, Bloch, Kd, Bolger, Af, Bøtker, He, Bozkurt, B, Bugiardini, R, Cannon, C, de Lemos, J, Eberli, Fr, Escobar, E, Hlatky, M, James, S, Kern, Kb, Moliterno, Dj, Mueller, C, Neskovic, An, Pieske, Bm, Schulman, Sp, Storey, Rf, Taubert, Ka, Vranckx, P, Wagner, D. R., Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD, Lindahl B, Morrow DA, Clemmensen PM, Johanson P, Hod H, Underwood R, Bax JJ, Bonow JJ, Pinto F, Gibbons RJ, Fox KA, Atar D, Newby LK, Galvani M, Hamm CW, Uretsky BF, Steg PG, Wijns W, Bassand JP, Menasche P, Ravkilde J, Ohman EM, Antman EM, Wallentin LC, Armstrong PW, Januzzi JL, Nieminen MS, Gheorghiade M, Filippatos G, Luepker RV, Fortmann SP, Rosamond WD, Levy D, Wood D, Smith SC, Hu D, Lopez-Sendon JL, Robertson RM, Weaver D, Tendera M, Bove AA, Parkhomenko AN, Vasilieva EJ, Mendis S, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Knuuti J, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Torbicki A, Vahanian A, Windecker S, Morais J, Aguiar C, Almahmeed W, Arnar DO, Barili F, Bloch KD, Bolger AF, Botker HE, Bozkurt B, Bugiardini R, Cannon C, de Lemos J, Eberli FR, Escobar E, Hlatky M, James S, Kern KB, Moliterno DJ, Mueller C, Neskovic AN, Pieske BM, Schulman SP, Storey RF, Taubert KA, Vranckx P, Wagner DR., Cardiology, lLindahl B, K. Thygesen, J. S. Alpert, A. S. Jaffe, M. L. Simoon, B. R. Chaitman, H. D. White, H. A. Katu, F. S. Apple, B. Lindahl, D. A. Morrow, P. M. Clemmensen, P. Johanson, H. Hod, R. Underwood, J. J. Bax, R. O. Bonow, F. Pinto, R. J. Gibbon, K. A. Fox, D. Atar, L. K. Newby, M. Galvani, C. W. Hamm, B. F. Uretsky, P. Gabriel Steg, W. Wijn, J.-P. Bassand, P. Menasche, J. Ravkilde, E. M. Ohman, E. M. Antman, L. C. Wallentin, P. W. Armstrong, J. L. Januzzi, M. S. Nieminen, M. Gheorghiade, G. Filippato, R. V. Luepker, S. P. Fortmann, W. D. Rosamond, D. Levy, D. Wood, S. C. Smith, D. Hu, J.-L. Lopez-Sendon, R. M. Robertson, D. Weaver, M. Tendera, A. A. Bove, A. N. Parkhomenko, E. J. Vasilieva, S. Mendi, H. Baumgartner, C. Ceconi, V. Dean, C. Deaton, R. Fagard, C. Funck-Brentano, D. Hasdai, A. Hoe, P. Kirchhof, J. Knuuti, P. Kolh, T. McDonagh, C. Moulin, B. A. Popescu, Z. Reiner, U. Sechtem, P. A. Sirne, A. Torbicki, A. Vahanian, S. Windecker, J. Morai, C. Aguiar, W. Almahmeed, D. O. Arnar, F. Barili, K. D. Bloch, A. F. Bolger, H. E. Botker, B. Bozkurt, R. Bugiardini, C. Cannon, J. de Lemo, F. R. Eberli, E. Escobar, M. Hlatky, S. Jame, K. B. Kern, D. J. Moliterno, C. Mueller, A. N. Neskovic, B. M. Pieske, S. P. Schulman, R. F. Storey, K. A. Taubert, P. Vranckx, D. R. Wagner, Thygesen, K, Alpert, J, Jaffe, A, Simoons, Ml, Chaitman, Br, White, Hd, Katus, Ha, Apple, F, Lindahl, B, Morrow, Da, Clemmensen, Pm, Johanson, P, Hod, H, Underwood, R, Bax, Jj, Bonow, Jj, Pinto, F, Gibbons, Rj, Fox, Ka, Atar, D, Newby, Lk, Galvani, M, Hamm, Cw, Uretsky, Bf, Steg, Pg, Wijns, W, Bassand, Jp, Menasche, P, Ravkilde, J, Ohman, Em, Antman, Em, Wallentin, Lc, Armstrong, Pw, Januzzi, Jl, Nieminen, M, Gheorghiade, M, Filippatos, G, Luepker, Rv, Fortmann, Sp, Rosamond, Wd, Levy, D, Wood, D, Smith, Sc, Hu, D, Lopez-Sendon, Jl, Robertson, Rm, Weaver, D, Tendera, M, Bove, Aa, Parkhomenko, An, Vasilieva, Ej, Mendis, S, Baumgartner, H, Ceconi, C, Dean, V, Deaton, C, Fagard, R, Funck-Brentano, C, Hasdai, D, Hoes, A, Kirchhof, P, Knuuti, J, Kolh, P, Mcdonagh, T, Moulin, C, Popescu, Ba, Reiner, Z, Sechtem, U, Sirnes, Pa, Torbicki, A, Vahanian, A, Windecker, S, Morais, J, Aguiar, C, Almahmeed, W, Arnar, Do, Barili, F, Bloch, Kd, Bolger, Af, Botker, He, Bozkurt, B, Bugiardini, R, Cannon, C, de Lemos, J, Eberli, Fr, Escobar, E, Hlatky, M, James, S, Kern, Kb, Moliterno, Dj, Mueller, C, Neskovic, An, Pieske, Bm, Schulman, Sp, Storey, Rf, Taubert, Ka, Vranckx, P, and Wagner, Dr
Subjects: High-sensitivity troponin, Ticagrelor, Chest pain unit, Quality Assurance, Health Care, Epidemiology, medicine.medical_treatment, Myocardial Infarction, Myocardial ischaemia, Global Health, Early invasive strategy, Electrocardiography, Stent, Myocardial Revascularization, Myocardial infarction, Coronary Artery Bypass, Intraoperative Complications, Left bundle branch block, Health Policy, Electrocardiography in myocardial infarction, Cangrelor, Stents, Acute coronary syndrome, Cardiology and Cardiovascular Medicine, Prasugrel, Diagnostic Imaging, medicine.medical_specialty, Public Policy, Risk Assessment, Vorapaxar, Percutaneous Coronary Intervention, Physiology (medical), Terminology as Topic, Humans, Enoxaparin, Bypass surgery, Community and Home Care, Heart Failure, Rhythm monitoring, Aspirin, Unstable angina, Angioplasty, Recommendation, ta3121, medicine.disease, Myocardial infarction diagnosis, Bivalirudin, Biomarkers, Time Factors, Platelet inhibition, Consensus Development Conferences as Topic, Diagnostic Techniques, Cardiovascular, Myocardial Ischemia, Guideline, Diabete, Nitrate, Left ventricular hypertrophy, Coronary artery disease, Rivaroxaban, Recurrence, Apixaban, Clinical Trials as Topic, Graft Occlusion, Vascular, Atherothrombosi, Acute cardiac care, Right bundle branch block, Clopidogrel, Dabigatran, Prosthesis Failure, AHA Scientific Statements, Practice Guidelines as Topic, Cardiology, Biological Markers, Radiology, Critical Care, Glycoprotein IIb/IIIa inhibitor, European Society of Cardiology, Diagnosis, Differential, Anticoagulation, Internal medicine, medicine, Beta-blocker, cardiovascular diseases, Heparin, business.industry, Revascularization, Cardiovascular Surgical Procedures, MYOCARDIAL INFARCTION, Statin, Percutaneous coronary intervention, Arrhythmias, Cardiac, Cardiac Imaging Techniques, Fondaparinux, Heart failure, Non-ST-elevation myocardial infarction, business
Abstract: ACCF : American College of Cardiology Foundation ACS : acute coronary syndrome AHA : American Heart Association CAD : coronary artery disease CABG : coronary artery bypass grafting CKMB : creatine kinase MB isoform cTn : cardiac troponin CT : computed tomography CV : coefficient of variation ECG : electrocardiogram ESC : European Society of Cardiology FDG : fluorodeoxyglucose h : hour(s) HF : heart failure LBBB : left bundle branch block LV : left ventricle LVH : left ventricular hypertrophy MI : myocardial infarction mIBG : meta-iodo-benzylguanidine min : minute(s) MONICA : Multinational MONItoring of trends and determinants in CArdiovascular disease) MPS : myocardial perfusion scintigraphy MRI : magnetic resonance imaging mV : millivolt(s) ng/L : nanogram(s) per litre Non-Q MI : non-Q wave myocardial infarction NSTEMI : non-ST-elevation myocardial infarction PCI : percutaneous coronary intervention PET : positron emission tomography pg/mL : pictogram(s) per millilitre Q wave MI : Q wave myocardial infarction RBBB : right bundle branch block sec : second(s) SPECT : single photon emission computed tomography STEMI : ST elevation myocardial infarction ST–T : ST-segment –T wave URL : upper reference limit WHF : World Heart Federation WHO : World Health Organization Myocardial infarction (MI) can be recognised by clinical features, including electrocardiographic (ECG) findings, elevated values of biochemical markers (biomarkers) of myocardial necrosis, and by imaging, or may be defined by pathology. It is a major cause of death and disability worldwide. MI may be the first manifestation of coronary artery disease (CAD) or it may occur, repeatedly, in patients with established disease. Information on MI rates can provide useful information regarding the burden of CAD within and across populations, especially if standardized data are collected in a manner that …
Published: 2012
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11. ACCURACY AND USEFULNESS OF ECHOVENTRICULOGRAPHY IN ACUTE MYOCARDIAL INFARCTION

Author: Heikkilä J and Nieminen Ms
Subjects: medicine.medical_specialty, Heart Ventricles, Myocardial Infarction, Autopsy, Electrocardiography, Clinical decision making, Internal medicine, Internal Medicine, medicine, Humans, Myocardial infarction, medicine.diagnostic_test, business.industry, Electrocardiography in myocardial infarction, medicine.disease, Myocardial Contraction, medicine.anatomical_structure, Echocardiography, Evaluation Studies as Topic, Ventricle, Acute Disease, Coronary care unit, Cardiology, Cineangiography, business
Abstract: Echoventriculography is a noninvasive and three-dimensional ultrasonic technique capable to assess in detail the regional performance of the left ventricle. Therefore the mechanical performance of the left ventricle after myocardial infarction is informatively assessed by the composite contributions made by infarcted and noninfarcted segments. Its reliability has been confirmed by direct cineangiographic and autopsy correlations. In clinical decision making such direct information is of great value both for diagnosis and therapeutic selection. In the coronary care unit echoventriculography provides most information obtained by the less feasible invasive cineangiographic examinations.
Published: 2009
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12. TECHNICAL ASPECTS OF SINGLE TRANSDUCER ECHOCARDIOGRAPHY

Author: Nieminen Ms
Subjects: Transducer, Scale (ratio), Echocardiography, business.industry, Acoustics, Transducers, Internal Medicine, Humans, Medicine, Wall motion, business
Abstract: SUMMARY In echocardiographic recordings optimal amplification and A-mode control should be used. In wall motion analysis greater accuracy is obtained by utilization of enlarged display scale. When these technical aspects are taken into consideration accurate and reproducible recordings are obtained.
Published: 2009
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13. Lowering Albuminuria—Does It Lower the Cardiovascular Risk?

Author: Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlo[Combining Diaeresis]f B, Devereux RB, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, and Wan Y
Subjects: Nephrology, General Medicine
Published: 2005
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14. Genetically Determined Height and Coronary Artery Disease

Author: Nelson,CP, Hamby,SE, Saleheen,D, Hopewell,JC, Zeng,L, Assimes,TL, Kanoni,S, Willenborg,C, Burgess,S, Amouyel,P, Anand,S, Blankenberg,S, Boehm,BO, Clarke,RJ, Collins,R, Dedoussis,G, Farrall,M, Franks,PW, Groop,L, Hall,AS, Hamsten,A, Hengstenberg,C, Hovingh,GK, Ingelsson,E, Kathiresan,S, Kee,F, König,IR, Kooner,J, Lehtimäki,T, März,W, McPherson,R, Metspalu,A, Nieminen,MS, O'Donnell,CJ, Palmer,CN, Peters,A, Perola,M, Reilly,MP, Ripatti,S, Roberts,R, Salomaa,V, Shah,SH, Schreiber,S, Siegbahn,A, Thorsteinsdottir,U, Veronesi,G, Wareham,N, Willer,CJ, Zalloua,PA, Erdmann,J, Deloukas,P, Watkins,H, Schunkert,H, Danesh,J, Thompson,JR, Samani,NJ, Assimes,T, Goldstein,BA, Stirrups,K, Cazier,JB, Johansson,Å, Lee,JY, Chambers,JC, Esko,T, Folkersen,L, Goel,A, Grundberg,E, Havulinna,AS, Ho,WK, Eriksson,N, Kleber,ME, Kristiansson,K, Lundmark,P, Lyytikäinen,LP, Rafelt,S, Shungin,D, Strawbridge,RJ, Thorleifsson,G, Tikkanen,E, Van, Zuydam, N, Voight,BF, Waite,LL, Zhang,W, Ziegler,A, Absher,D, Altshuler,D, Balmforth,AJ, Barroso,I, Braund,PS, Burgdorf,C, Claudi Boehm,S, Cox,D, Dimitriou,M, Do,R, Doney,AS, El, Mokhtari, Eriksson,P, Fischer,K, Fontanillas,P, Franco Cereceda,A, Gigante,B, Gustafsson,S, Hager,J, Hallmans,G, Han,BG, Hunt,SE, Kang,HM, Illig,T, Kessler,T, Knowles,JW, Kolovou,G, Kuusisto,J, Langenberg,C, Langford,C, Leander,K, Lokki,ML, Lundmark,A, McCarthy,MI, Meisinger,C, Melander,O, Mihailov,E, Maouche,S, Morris,AD, Müller Nurasyid,M, Nikus,K, Peden,JF, Rayner,NW, Rasheed,A, Rosinger,S, Rubin,D, Rumpf,MP, Schäfer,A, Sivananthan,M, Song,C, Stewart,AF, Tan,ST, Thorgeirsson,G, van, der, Schoot, CE, Wagner,PJ, Wells,GA, Wild,PS, Yang,TP, Arveiler,D, Basart,H, Boehnke,M, Boerwinkle,E, BRAMBILLA, PAOLO, Cambien,F, Cupples,AL, de, Faire, U, Dehghan,A, Diemert,P, Epstein,SE, Evans,A, Ferrario,MM, Ferrières,J, Gauguier,D, Go,AS, Goodall,AH, Gudnason,V, Hazen,SL, Holm,H, Iribarren,C, Jang,Y, Kähönen,M, Kim,HS, Klopp,N, Koenig,W, Kratzer,W, Kuulasmaa,K, Laakso,M, Laaksonen,R, Lind,L, Ouwehand,WH, Parish,S, Park,JE, Pedersen,NL, Quertermous,T, Rader,DJ, Schadt,E, Sinisalo,J, Stark,K, Stefansson,K, Trégouët,DA, Virtamo,J, Wallentin,L, Zimmermann,ME, Sandhu,MS, Pastinen,T, Syvänen,AC, Blankenberg,SS, Clarke,R, O'Donnell,C, Kooner,JS, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Clinical Haematology, Other departments, Lee Kong Chian School of Medicine (LKCMedicine), Nelson, C, Hamby, S, Saleheen, D, Hopewell, J, Zeng, L, Assimes, T, Kanoni, S, Willenborg, C, Burgess, S, Amouyel, P, Anand, S, Blankenberg, S, Boehm, B, Clarke, R, Collins, R, Dedoussis, G, Farrall, M, Franks, P, Groop, L, Hall, A, Hamsten, A, Hengstenberg, C, Hovingh, G, Ingelsson, E, Kathiresan, S, Kee, F, König, I, Kooner, J, Lehtimäki, T, März, W, Mcpherson, R, Metspalu, A, Nieminen, M, O'Donnell, C, Palmer, C, Peters, A, Perola, M, Reilly, M, Ripatti, S, Roberts, R, Salomaa, V, Shah, S, Schreiber, S, Siegbahn, A, Thorsteinsdottir, U, Veronesi, G, Wareham, N, Willer, C, Zalloua, P, Erdmann, J, Deloukas, P, Watkins, H, Schunkert, H, Danesh, J, Thompson, J, Samani, N, Goldstein, B, Stirrups, K, Cazier, J, Johansson, Å, Lee, J, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van, Z, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El, M, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, G, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, Van, D, Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, De, F, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Quertermous, T, Rader, D, Schadt, E, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Sandhu, M, Pastinen, T, Syvänen, A, Burgess, Stephen [0000-0001-5365-8760], Wareham, Nicholas [0000-0003-1422-2993], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
Subjects: systolic blood pressure, Pathology, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, genetic association, genotype, cholesterol blood level, insulin blood level, Coronary Artery Disease, 030204 cardiovascular system & hematology, genetic risk, Triglyceride, low density lipoprotein cholesterol, Coronary artery disease, 0302 clinical medicine, high density lipoprotein cholesterol, single nucleotide polymorphism, Risk Factors, genetic variability, Odds Ratio, hyperlipidemia, Science::Medicine [DRNTU], genetics, glucose, risk, 0303 health sciences, medicine.diagnostic_test, non insulin dependent diabetes mellitus, Medicine (all), allele, insulin, triacylglycerol, triacylglycerol, adult, aged, Article, atherosclerosis, bioinformatics, body height, body mass, cardiovascular risk, controlled study, coronary artery disease, development, diastolic blood pressure, female, glucose blood level, human, major clinical study, male, mean arterial pressure, priority journal, pulse pressure, risk factor, smoking, triacylglycerol blood level, blood, complication, risk, Adult, Body Height, Cholesterol, LDL, Genetic Variation, Humans, Hyperlipidemias, Triglycerides, General Medicine, Cholesterol, Cardiology, Adult, medicine.medical_specialty, Inverse Association, Single-nucleotide polymorphism, Endocrinology and Diabetes, LDL, 03 medical and health sciences, Internal medicine, medicine, Risk factor, 030304 developmental biology, Genetic association, business.industry, Odds ratio, medicine.disease, Lipid profile, business, Body mass index
Abstract: BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P
Published: 2015

15. Clinical picture and risk prediction of short-term mortality in cardiogenic shock (vol 17, pg 501, 2015)

Author: Harjola, VP, Lassus, J, Sionis, A, Kober, L, Tarvasmaki, T, Spinar, J, Parissis, J, Banaszewski, M, Silva-Cardoso, J, Carubelli, V, Di Somma, S, Tolppanen, H, Zeymer, U, Thiele, H, Nieminen, MS, and Mebazaa, A
Published: 2015

16. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders

Author: den Hoed, M, Eijgelsheim, M, Esko, T, Brundel, Bj, Peal, Ds, Evans, Dm, Nolte, Im, Segrè, Av, Holm, H, Handsaker, Re, Westra, Hj, Johnson, T, Isaacs, A, Yang, J, Lundby, A, Zhao, Jh, Kim, Yj, Go, Mj, Almgren, P, Bochud, M, Boucher, G, Cornelis, Mc, Gudbjartsson, D, Hadley, D, van der Harst, P, Hayward, C, den Heijer, M, Igl, W, Jackson, Au, Kutalik, Z, Luan, J, Kemp, Jp, Kristiansson, K, Ladenvall, C, Lorentzon, M, Montasser, Me, Njajou, Ot, O'Reilly, Pf, Padmanabhan, S, St Pourcain, B, Rankinen, T, Salo, P, Tanaka, T, Timpson, Nj, Vitart, V, Waite, L, Wheeler, W, Zhang, W, Draisma, Hh, Feitosa, Mf, Kerr, Kf, Lind, Pa, Mihailov, E, Onland Moret NC, Song, C, Weedon, Mn, Xie, W, Yengo, L, Absher, D, Albert, Cm, Alonso, A, Arking, De, de Bakker PI, Balkau, B, Barlassina, C, Benaglio, P, Bis, Jc, Bouatia Naji, N, Brage, S, Chanock, Sj, Chines, Ps, Chung, M, Darbar, D, Dina, C, Dörr, M, Elliott, P, Felix, Sb, Fischer, K, Fuchsberger, C, de Geus EJ, Goyette, P, Gudnason, V, Harris, Tb, Hartikainen, Al, Havulinna, As, Heckbert, Sr, Hicks, Aa, Hofman, A, Holewijn, S, Hoogstra Berends, F, Hottenga, Jj, Jensen, Mk, Johansson, A, Junttila, J, Kääb, S, Kanon, B, Ketkar, S, Khaw, Kt, Knowles, Jw, Kooner, As, Kors, Ja, Kumari, M, Milani, L, Laiho, P, Lakatta, Eg, Langenberg, C, Leusink, M, Liu, Y, Luben, Rn, Lunetta, Kl, Lynch, Sn, Markus, Mr, Marques Vidal, P, Mateo Leach, I, Mcardle, Wl, Mccarroll, Sa, Medland, Se, Miller, Ka, Montgomery, Gw, Morrison, Ac, Müller Nurasyid, M, Navarro, P, Nelis, M, O'Connell, Jr, O'Donnell, Cj, Ong, Kk, Newman, Ab, Peters, A, Polasek, O, Pouta, A, Pramstaller, Pp, Psaty, Bm, Rao, Dc, Ring, Sm, Rossin, Ej, Rudan, D, Sanna, S, Scott, Ra, Sehmi, Js, Sharp, S, Shin, Jt, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stewart, C, Stringham, Hm, Tarasov, Kv, Uitterlinden, Ag, Vandenput, L, Hwang, Sj, Whitfield, Jb, Wijmenga, C, Wild, Sh, Willemsen, G, Wilson, Jf, Witteman, Jc, Wong, A, Wong, Q, Jamshidi, Y, Zitting, P, Boer, Jm, Boomsma, Di, Borecki, Ib, van Duijn CM, Ekelund, U, Forouhi, Ng, Froguel, P, Hingorani, A, Ingelsson, E, Kivimaki, M, Kronmal, Ra, Kuh, D, Lind, L, Martin, Ng, Oostra, Ba, Pedersen, Nl, Quertermous, T, Rotter, Ji, van der Schouw YT, Verschuren, Wm, Walker, M, Albanes, D, Arnar, Do, Assimes, Tl, Bandinelli, S, Boehnke, M, de Boer RA, Bouchard, C, Caulfield, Wl, Chambers, Jc, Curhan, G, Cusi, D, Eriksson, J, Ferrucci, L, van Gilst WH, Glorioso, N, de Graaf, J, Groop, L, Gyllensten, U, Hsueh, Wc, Hu, Fb, Huikuri, Hv, Hunter, Dj, Iribarren, C, Isomaa, B, Jarvelin, Mr, Jula, A, Kähönen, M, Kiemeney, La, van der Klauw MM, Kooner, Js, Kraft, P, Iacoviello, Licia, Lehtimäki, T, Lokki, Ml, Mitchell, Bd, Navis, G, Nieminen, Ms, Ohlsson, C, Poulter, Nr, Qi, L, Raitakari, Ot, Rimm, Eb, Rioux, Jd, Rizzi, F, Rudan, I, Salomaa, V, Sever, Ps, Shields, Dc, Shuldiner, Ar, Sinisalo, J, Stanton, Av, Stolk, Rp, Strachan, Dp, Tardif, Jc, Thorsteinsdottir, U, Tuomilehto, J, van Veldhuisen DJ, Virtamo, J, Viikari, J, Vollenweider, P, Waeber, G, Widen, E, Cho, Ys, Olsen, Jv, Visscher, Pm, Willer, C, Franke, L, Global BPgen Consortium, Cardiogram, Consortium, Erdmann, J, Thompson, Jr, PR GWAS Consortium, Pfeufer, A, QRS GWAS Consortium, Sotoodehnia, N, QT IGC Consortium, Newton Cheh, C, CHARGE AF Consortium, Ellinor, Pt, Stricker, Bh, Metspalu, A, Perola, M, Beckmann, Js, Smith, Gd, Stefansson, K, Wareham, Nj, Munroe, Pb, Sibon, Oc, Milan, Dj, Snieder, H, Samani, Nj, Loos, R. J., Global BPgen Consortium, CARDIoGRAM Consortium, PR GWAS Consortium, QRS GWAS Consortium, QT-IGC Consortium, CHARGE-AF Consortium, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Imaging Technology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Humane Biologie, Epidemiology, Public Health, Clinical Genetics, Surgery, Medical Informatics, Internal Medicine, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, ICaR - Circulation and metabolism, EMGO - Lifestyle, overweight and diabetes, NCA - Brain imaging technology, ACS - Heart failure & arrhythmias, Physiology, Internal medicine, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Molecular Neuroscience and Ageing Research (MOLAR), and Stem Cell Aging Leukemia and Lymphoma (SALL)
Subjects: Netherlands Twin Register (NTR), Aetiology, screening and detection [ONCOL 5], 030204 cardiovascular system & hematology, Arrhythmias, DISEASE, Sudden cardiac death, PR INTERVAL, 0302 clinical medicine, Gene Frequency, Heart Rate, Arrhythmias, Cardiac/genetics, 0303 health sciences, COMMON VARIANTS, Dilated cardiomyopathy, Atrial fibrillation, Single Nucleotide, Heart Rate/genetics, 3. Good health, DROSOPHILA, LIBRARY, Cardiology, QRS DURATION, Electrical conduction system of the heart, Metabolic Networks and Pathways, rhytm, conduction, gene, medicine.medical_specialty, SUSCEPTIBILITY LOCI, Quantitative Trait Loci, Cardiac/genetics, Biology, Polymorphism, Single Nucleotide, Article, Sick sinus syndrome, Heart Conduction System/physiopathology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Heart Conduction System, Internal medicine, Cardiac conduction, Heart rate, Genetics, medicine, Animals, Humans, GENOME-WIDE ASSOCIATION, Polymorphism, Health aging / healthy living Cardiovascular diseases [IGMD 5], Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 030304 developmental biology, QT INTERVAL, Arrhythmias, Cardiac, ta3121, medicine.disease, Endocrinology, Genetic Loci, Heart failure, ATRIAL-FIBRILLATION, Genome-Wide Association Study
Abstract: Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets. © 2013 Nature America, Inc. All rights reserved.
Published: 2013
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17. Erratum: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution (Nature Genetics (2010) 42 (949-960))

Author: Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Steinthorsdottir, V, Thorleifsson, G, Zillikens, MC, Speliotes, EK, Mägi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, J, Vedantam, S, Esko, T, Kilpeläinen, TO, Kutalik, Z, Li, S, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, L, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Estrada, K, Goddard, ME, Lettre, G, Mangino, M, Nyholt, DR, Purcell, S, Vernon Smith, A, Visscher, PM, Yang, J, McCarroll, SA, Nemesh, J, Voight, BF, Absher, D, Amin, N, Aspelund, T, Coin, L, Glazer, NL, Hayward, C, Heard-Costa, NL, Hottenga, J-J, Johansson, A, Johnson, T, Kaakinen, M, Kapur, K, Ketkar, S, Knowles, JW, Kraft, P, Kraja, AT, Lamina, C, Leitzmann, MF, McKnight, B, Morris, AP, Ong, KK, Perry, JRB, Peters, MJ, Polasek, O, Prokopenko, I, Rayner, NW, Ripatti, S, Rivadeneira, F, Robertson, NR, Sanna, S, Sovio, U, Surakka, I, Teumer, A, Van Wingerden, S, Vitart, V, Zhao, JH, Cavalcanti-Proença, C, Chines, PS, Fisher, E, Kulzer, JR, Lecoeur, C, Narisu, N, Sandholt, C, Scott, LJ, Silander, K, Stark, K, Tammesoo, M-L, Teslovich, TM, Timpson, NJ, Watanabe, RM, Welch, R, Chasman, DI, Cooper, MN, Jansson, J-O, Kettunen, J, Lawrence, RW, Pellikka, N, Perola, M, Vandenput, L, Alavere, H, Almgren, P, Atwood, LD, Bennett, AJ, Biffar, R, Bonnycastle, LL, Bornstein, SR, Buchanan, TA, Campbell, H, Day, INM, Dei, M, Dörr, M, Elliott, P, Erdos, MR, Eriksson, JG, Freimer, NB, Fu, M, Gaget, S, Geus, EJC, Gjesing, AP, Grallert, H, Gräßler, J, Groves, CJ, Guiducci, C, Hartikainen, A-L, Hassanali, N, Havulinna, AS, Herzig, K-H, Hicks, AA, Hui, J, Igl, W, Jousilahti, P, Jula, A, Kajantie, E, Kinnunen, L, Kolcic, I, Koskinen, S, Kovacs, P, Kroemer, HK, Krzelj, V, Kuusisto, J, Kvaloy, K, Laitinen, J, Lantieri, O, Lathrop, GM, Lokki, M-L, Luben, RN, Ludwig, B, McArdle, WL, McCarthy, A, Morken, MA, Nelis, M, Neville, MJ, Paré, G, Parker, AN, Peden, JF, Pichler, I, Pietiläinen, KH, Platou, CGP, Pouta, A, Ridderstråle, M, Samani, NJ, Saramies, J, Sinisalo, J, Smit, JH, Strawbridge, RJ, Stringham, HM, Swift, AJ, Teder-Laving, M, Thomson, B, Usala, G, Van Meurs, JBJ, Van Ommen, G-J, Vatin, V, Volpato, CB, Wallaschofski, H, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Witte, DR, Zgaga, L, Zitting, P, Beilby, JP, James, AL, Kähönen, M, Lehtimäki, T, Nieminen, MS, Ohlsson, C, Palmer, LJ, Raitakari, O, Ridker, PM, Stumvoll, M, Tönjes, A, Viikari, J, Balkau, B, Ben-Shlomo, Y, Bergman, RN, Boeing, H, Smith, GD, Ebrahim, S, Froguel, P, Hansen, T, Hengstenberg, C, Hveem, K, Isomaa, B, Jørgensen, T, Karpe, F, Khaw, K-T, Laakso, M, Lawlor, DA, Marre, M, Meitinger, T, Metspalu, A, Midthjell, K, Pedersen, O, Salomaa, V, Schwarz, PEH, Tuomi, T, Tuomilehto, J, Valle, TT, Wareham, NJ, Arnold, AM, Beckmann, JS, Bergmann, S, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Collins, FS, Eiriksdottir, G, Gudnason, V, Gyllensten, U, Hamsten, A, Hattersley, AT, Hofman, A, Hu, FB, Illig, T, Iribarren, C, Jarvelin, M-R, Kao, WHL, Kaprio, J, Launer, LJ, Munroe, PB, Oostra, B, Penninx, BW, Pramstaller, PP, Psaty, BM, Quertermous, T, Rissanen, A, Rudan, I, Shuldiner, AR, Soranzo, N, Spector, TD, Syvanen, A-C, Uda, M, Uitterlinden, A, Völzke, H, Vollenweider, P, Wilson, JF, Witteman, JC, Wright, AF, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Frayling, TM, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, North, KE, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, Hirschhorn, JN, Assimes, TL, Wichmann, H-E, Thorsteinsdottir, U, Van Duijn, CM, Stefansson, K, Cupples, LA, Loos, RJF, Barroso, I, McCarthy, MI, Fox, CS, Mohlke, KL, and Lindgren, CM
Published: 2011

18. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author: Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, Bouatia Naji, N, Dimas, As, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, Cs, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, Kerr Conte, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, Martínez Larrad MT, Narisu, N, Nastase Mannila, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, van 't Hooft FM, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, Serrano Ríos, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, Fs, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, Voight BF, Florez J. C., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Ys, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, Mulic, R, Ngwa, Js, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, Ms, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, Ds, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, Is, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, Ms, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, Js, Boeing, H, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository
Subjects: Male, Netherlands Twin Register (NTR), endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medizin, Genome-wide association study, Type 2 diabetes, CORONARY HEART-DISEASE, Fasting/blood, 0302 clinical medicine, Insulin, Glucose homeostasis, ddc:576.5, Genome-wide, Diabetes Mellitus, Type 2/blood/genetics/metabolism, CARDIoGRAM Consortium, POPULATION, Proinsulin, RISK, Genetics, 0303 health sciences, INSULIN SENSITIVITY, 11 Medical And Health Sciences, Fasting, Polymorphism, Single Nucleotide/genetics, OBESITY, Female, type 2 diabetes, Life Sciences & Biomedicine, hormones, hormone substitutes, and hormone antagonists, Insulin processing, Adult, medicine.medical_specialty, endocrine system, ENDOCRINOLOGY & METABOLISM, SUSCEPTIBILITY LOCI, Genotype, 030209 endocrinology & metabolism, DIAGRAM Consortium, Biology, C4D Consortium, Polymorphism, Single Nucleotide, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Insulin resistance, BETA-CELL FUNCTION, SDG 3 - Good Health and Well-being, Internal medicine, GIANT Consortium, Internal Medicine, medicine, Humans, METAANALYSIS, 030304 developmental biology, Science & Technology, Genome, Human, Hormonal regulation [IGMD 6], Genetic Variation, nutritional and metabolic diseases, proinsulin, medicine.disease, Proinsulin/blood, TCF7L2, Endocrinology, Diabetes Mellitus, Type 2, MuTHER Consortium, GLUCOSE-HOMEOSTASIS, Insulin/blood
Abstract: OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.
Published: 2011
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19. Geographic Variation in Clinical Course Among Patients Hospitalized for Acute Heart Failure: Insights From ASCEND-HF

Author: Metra, Marco, Hernandez, Af, Heizer, Gm, Clausell, N, Corbalan, R, Costanzo, Mr, Dunlap, Me, Ezekowitz, Ja, Howlett, Jg, Krum, H, Voors, Aa, Armstrong, Pw, Massie, Bm, Nieminen, Ms, Komajda, M, Mcmurray, Jj, Swedberg, K, Starling, Rc, O'Connor, Cm, Califf, Rm, and Teerlink, Jr
Published: 2011

20. New genetic loci link adipose and insulin biology to body fat distribution.

Author: ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., Carlson, OD., Egan, JM., Böhringer, S., van Heemst, D., Kedenko, L., Kristiansson, K., Nuotio, ML., Loo, BM., Harris, T., Garcia, M., Kanaya, A., Haun, M., Klopp, N., Wichmann, HE., Deloukas, P., Katsareli, E., Couper, DJ., Duncan, BB., Kloppenburg, M., Adair, LS., Borja, JB., Wilson, JG., Musani, S., Guo, X., Johnson, T., Semple, R., Teslovich, TM., Allison, MA., Redline, S., Buxbaum, SG., Mohlke, KL., Meulenbelt, I., Ballantyne, CM., Dedoussis, GV., Hu, FB., Liu, Y., Paulweber, B., Spector, TD., Slagboom, P., Ferrucci, L., Jula, A., Perola, M., Raitakari, O., Florez, JC., Salomaa, V., Eriksson, JG., Frayling, TM., Hicks, AA., Lehtimäki, T., Smith, GD., Siscovick, DS., Kronenberg, F., van Duijn, C., Loos, RJ., Waterworth, DM., Meigs, JB., Dupuis, J., Richards, JB., Willenborg, C., Farrall, M., Assimes, TL., Thompson, JR., Ingelsson, E., Saleheen, D., Erdmann, J., Goldstein, BA., Stirrups, K., König, IR., Cazier, JB., Johansson£££Åsa£££ Å., Hall, AS., Lee, JY., Willer, CJ., Chambers, JC., Esko£££Tõnu£££ T., Folkersen, L., Goel, A., Grundberg, E., Havulinna, AS., Ho, WK., Hopewell, JC., Eriksson, N., Kleber, ME., Lundmark, P., Lyytikäinen, LP., Rafelt, S., Shungin, D., Strawbridge, RJ., Thorleifsson, G., Tikkanen, E., Van Zuydam, N., Voight, BF., Waite, LL., Zhang, W., Ziegler, A., Absher, D., Altshuler, D., Balmforth, AJ., Barroso£££Inês£££ I., Braund, PS., Burgdorf, C., Claudi-Boehm, S., Cox, D., Dimitriou, M., Do, R., Doney, AS., El Mokhtari, N., Eriksson, P., Fischer, K., Fontanillas, P., Franco-Cereceda, A., Gigante, B., Groop, L., Gustafsson, S., Hager, J., Hallmans, G., Han, BG., Hunt, SE., Kang, HM., Illig, T., Kessler, T., Knowles, JW., Kolovou, G., Kuusisto, J., Langford, C., Leander, K., Lokki, ML., Lundmark, A., McCarthy, MI., Meisinger, C., Melander, O., Mihailov, E., Maouche, S., Morris, AD., Müller-Nurasyid, M., Nikus, K., Peden, JF., Rayner, NW., Rasheed, A., Rosinger, S., Rubin, D., Rumpf, MP., Schäfer, A., Sivananthan, M., Song, C., Stewart, AF., Tan, ST., Thorgeirsson, G., van der Schoot CE., Wagner, PJ., Wells, GA., Wild, PS., Yang, TP., Amouyel, P., Arveiler, D., Basart, H., Boehnke, M., Boerwinkle, E., Brambilla, P., Cambien, F., Cupples, AL., de Faire, U., Dehghan, A., Diemert, P., Epstein, SE., Evans, A., Ferrario, MM., Ferrières, J., Gauguier, D., Go, AS., Goodall, AH., Gudnason, V., Hazen, S., Holm, H., Iribarren, C., Jang, Y., Kee, F., Kim, HS., Koenig, W., Kratzer, W., Kuulasmaa, K., Laakso, M., Laaksonen, R., Lind, L., Ouwehand, WH., Parish, S., Park, JE., Pedersen, NL., Peters, A., Quertermous, T., Rader, DJ., Schadt, E., Shah, SH., Sinisalo, J., Stark, K., Stefansson, K., Trégouët, DA., Virtamo, J., Wallentin, L., Wareham, N., Zimmermann, ME., Nieminen, MS., Hengstenberg, C., Sandhu, MS., Pastinen, T., Syvänen, AC., Hovingh, GK., Dedoussis, G., Franks, PW., Metspalu, A., Zalloua, PA., Siegbahn, A., Schreiber, S., Ripatti, S., Blankenberg, SS., Clarke, R., Boehm, BO., O'Donnell, C., Reilly, MP., 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K.L.
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

21. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Author: Winkler, TW, Justice, AE, Graff, M, Barata, L, Feitosa, MF, Chu, S, Czajkowski, J, Esko, T, Fall, T, Kilpelainen, TO, Lu, YC, Magi, R, Mihailov, E, Pers, TH, Rueger, S, Teumer, A, Ehret, GB, Ferreira, T, Heard-Costa, NL, Karjalainen, J, Lagou, V, Mahajan, A, Neinast, MD, Prokopenko, I, Simino, J, Teslovich, TM, Jansen, R, Westra, HJ, White, CC, Absher, D, Ahluwalia, TS, Ahmad, Shahzad, Albrecht, E, Alves, AC, Bragg-Gresham, JL, de Craen, AJM, Bis, JC, Bonnefond, A, Boucher, G, Cadby, G, Cheng, YC, Chiang, CWK, Delgado, G, Demirkan, Ayse, Dueker, N, Eklund, N, Eiriksdottir, G, Eriksson, J, Feenstra, B, Fischer, K (Kirsten), Frau, F, Galesloot, TE, Geller, F, Goel, A, Gorski, M, Grammer, TB, Gustafsson, S, Haitjema, S, Hottenga, JJ (Jouke Jan), Huffman, JE, Jackson, AU, Jacobs, KB, Johansson, A, Kaakinen, M, Kleber, ME, Lahti, J, Leach, IM, Lehne, B, Liu, YF, Lo, KS, Lorentzon, M, Luan, J, Madden, PAF, Mangino, M, McKnight, B, Medina Gomez, Maria, Monda, KL, Montasser, ME, Muller, G, Muller-Nurasyid, M, Nolte, IM (Ilja), Panoutsopoulou, K, Pascoe, L, Paternoster, L, Rayner, NW, Renstrom, F, Rizzi, F, Rose, LM, Ryan, KA, Salo, P, Sanna, S, Scharnagl, H, Shi, JX, Smith, AV, Southam, L, Stancakova, A, Steinthorsdottir, V, Strawbridge, RJ, Sung, YJ, Tachmazidou, I, Tanaka, T, Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, 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M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, 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Thorleifsson, G, Trompet, S, Pervjakova, N, Tyrer, JP, Vandenput, L, Laan, Sander, van der Velde, Nathalie, van Setten, J, van Vliet-Ostaptchouk, JV, Verweij, N (Niek), Vlachopoulou, E, Waite, LL, Wang, SR, Wang, ZM, Wild, SH, Willenborg, C, Wilson, JF, Wong, A, Yang, Jiaqi, Yengo, L, Yerges-Armstrong, LM, Yu, L, Zhang, WH, Zhao, JH, Andersson, EA, Bakker, SJL, Baldassarre, D, Banasik, K, Barcella, M, Barlassina, C, Bellis, C, Benaglio, P, Blangero, J, Bluher, M, Bonnet, F, Bonnycastle, LL, Boyd, HA, Bruinenberg, M, Buchman, AS, Campbell, H, Chen, YDI, Chines, PS, Claudi-Boehm, S, Cole, J, Collins, FS, de Geus, EJC, de Groot, LCPGM (Lisette), Dimitriou, M, Duan, J, Enroth, S, Eury, E, Farmaki, AE, Forouhi, NG, Friedrich, N, Gejman, PV, Gigante, B, Glorioso, N, Go, AS, Gottesman, O, Grassler, J, Grallert, H, Grarup, N, Gu, YM, Broer, Linda, Ham, Annelies, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, N, Hattersley, AT, Heath, AC, Henders, AK, Hernandez, D, Hillege, H, Holmen, O, Hovingh, KG, Hui, J, Husemoen, LL, Hutri-Kahonen, N, Hysi, PG, Illig, T, De Jager, PL, Jalilzadeh, S, Jorgensen, T, Jukema, JW, Juonala, M, Kanoni, S, Karaleftheri, M, Khaw, KT, Kinnunen, L, Kittner, SJ, Koenig, W, Kolcic, I, Kovacs, P, Krarup, NT, Kratzer, W, Kruger, J, Kuh, D, Kumari, M, Kyriakou, T, Langenberg, C, Lannfelt, L, Lanzani, C, Lotay, V, Launer, LJ (Lenore), Leander, K, Lindstrom, J, Linneberg, A, Liu, YP, Lobbens, S, Luben, R, Lyssenko, V, Mannisto, S, Magnusson, PK, McArdle, WL, Menni, C, Merger, S, Milani, L, Montgomery, GW, Morris, AP, Narisu, N, Nelis, M, Ong, KK, Palotie, A, Perusse, L, Pichler, I, Pilia, MG, Pouta, A, Rheinberger, M, Ribel-Madsen, R, Richards, M, Rice, KM, Rice, TK, Rivolta, C, Salomaa, V, Sanders, AR, Sarzynski, MA, Scholtens, s, Scott, RA, Scott, WR, Sebert, S, Sengupta, S, Sennblad, B, Seufferlein, T, Silveira, A, Slagboom, PE (Eline), Smit, JH, Sparso, TH, Stirrups, K, Stolk, RP (Ronald), Stringham, HM, Swertz, MA, Swift, AJ, Syvanen, AC, Tan, ST, Thorand, B, Tonjes, A, Tremblay, A, Tsafantakis, E, van der Most, PJ, Volker, U, Vohl, MC, Vonk, JM, Waldenberger, M, Walker, RW, Wennauer, R, Widen, E, Willemsen, G, Wilsgaard, T, Wright, AF, Zillikens, M.C., Boon - van Dijk, Suzanne, Schoor, NM, Asselbergs, FW, de Bakker, PIW, Beckmann, JS, Beilby, J, Bennett, DA, Bergman, RN, Bergmann, S, Boger, CA, Boehm, BO, Boerwinkle, E, Boomsma, DI, Bornstein, SR, Bottinger, EP, Bouchard, C, Chambers, JC, Chanock, SJ, Chasman, DI, Cucca, F, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, JG, Evans, DA, de Faire, U, Farrall, M, Ferrucci, L, Ford, I, Franke, L, Franks, PW, Froguel, P, Gansevoort, RT, Gieger, C, Gronberg, H, Gudnason, V, Gyllensten, U, Hall, P, Hamsten, A, van der Harst, P, Hayward, C, Heliovaara, M, Hengstenberg, C, Hicks, AA, Hingorani, A, Hofman, Bert, Hu, F, Huikuri, HV, Hveem, K, James, AL, Jordan, JM, Jula, A, Kahonen, M, Kajantie, E, Kathiresan, S, Kiemeney, LALM, Kivimaki, M, Knekt, PB, Koistinen, HA, Kooner, JS, Koskinen, S, Kuusisto, J, Maerz, W, Martin, NG, Laakso, M, Lakka, TA, Lehtimaki, T, Lettre, G, Levinson, DF, Lind, L, Lokki, ML, Mantyselka, P, Melbye, M, Metspalu, A, Mitchell, BD, Moll, FL, Murray, JC, Musk, AW, Nieminen, MS, Njolstad, I, Ohlsson, C, Oldehinkel, AJ (A.), Oostra, Ben, Palmer, LJ, Pankow, JS, Pasterkamp, G, Pedersen, NL, Pedersen, O, Penninx, BW, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Psaty, BM, Qi, L, Quertermous, T, Raitakari, OT, Rankinen, T, Rauramaa, R, Ridker, PM, Rioux, JD, Rivadeneira, Fernando, Rotter, JI, Rudan, I, den Ruijter, HM, Saltevo, J, Sattar, N, Schunkert, H, Schwarz, PEH, Shuldiner, AR, Sinisalo, J, Snieder, H, Sorensen, TIA, Spector, TD, Staessen, JA, Stefania, B, Thorsteinsdottir, U, Stumvoll, M, Tardif, JC, Tremoli, E, Tuomilehto, J, Uitterlinden, André, Uusitupa, M, Verbeek, ALM, Vermeulen, SH, Viikari, JS, Vitart, V, Volzke, H, Vollenweider, P, Waeber, G, Walker, M, Wallaschofski, H, Wareham, NJ, Watkins, H, Zeggini, E, Chakravarti, A, Clegg, DJ, Cupples, LA, Gordon-Larsen, P, Jaquish, CE, Rao, DC, Abecasis, GR, Assimes, TL, Barroso, I, Berndt, SI, Boehnke, M, Deloukas, P, Fox, CS, Groop, LC, Hunter, DJ, Ingelsson, E, Kaplan, RC, McCarthy, MI, Mohlke, KL, O'Connell, JR, Schlessinger, D, Strachan, DP, Stefansson, K, Duijn, Cornelia, Hirschhorn, JN, Lindgren, CM, Heid, IM, North, KE, Borecki, IB, Kutalik, Z, and Loos, RJF
Abstract: Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men <= 50y, men > 50y, women <= 50y, women > 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR< 5%) age-specific effects, of which 11 had larger effects in younger (< 50y) than in older adults (>= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shap
Published: 2015

22. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, Harris, T, Hattersley, A, Heliövaara, M, Hicks, A, Hingorani, A, Hoffmann, W, Hofman, A, Homuth, G, Humphries, S, Hyppönen, E, Illig, T, Jarvelin, M, Johansen, B, Jousilahti, P, Jula, A, Kaprio, J, Kee, F, Keinanen Kiukaanniemi, S, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lyssenko, V, Männistö, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Musk, A, Möhlenkamp, S, Morris, A, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Palmer, L, Penninx, B, Peters, A, Pramstaller, P, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Shuldiner, A, Staessen, J, Steinthorsdottir, V, Stolk, R, Strauch, K, Tönjes, A, Tremblay, A, Tremoli, E, Vohl, M, Völker, U, Vollenweider, P, Wilson, J, Witteman, J, Adair, L, Bochud, M, Boehm, B, Bornstein, S, Bouchard, C, Cauchi, S, Caulfield, M, Chambers, J, Chasman, D, 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Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

23. Genetically determined height and coronary artery disease

Author: Nelson, C, Hamby, S, Saleheen, D, Hopewell, J, Zeng, L, Assimes, T, Kanoni, S, Willenborg, C, Burgess, S, Amouyel, P, Anand, S, Blankenberg, S, Boehm, B, Clarke, R, Collins, R, Dedoussis, G, Farrall, M, Franks, P, Groop, L, Hall, A, Hamsten, A, Hengstenberg, C, Hovingh, G, Ingelsson, E, Kathiresan, S, Kee, F, König, I, Kooner, J, Lehtimäki, T, März, W, Mcpherson, R, Metspalu, A, Nieminen, M, O'Donnell, C, Palmer, C, Peters, A, Perola, M, Reilly, M, Ripatti, S, Roberts, R, Salomaa, V, Shah, S, Schreiber, S, Siegbahn, A, Thorsteinsdottir, U, Veronesi, G, Wareham, N, Willer, C, Zalloua, P, Erdmann, J, Deloukas, P, Watkins, H, Schunkert, H, Danesh, J, Thompson, J, Samani, N, Goldstein, B, Stirrups, K, Cazier, J, Johansson, Å, Lee, J, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van, Z, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El, M, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, G, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, Van, D, Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, De, F, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Quertermous, T, Rader, D, Schadt, E, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Sandhu, M, Pastinen, T, Syvänen, A, Nelson,CP, Hamby,SE, Saleheen,D, Hopewell,JC, Zeng,L, Assimes,TL, Kanoni,S, Willenborg,C, Burgess,S, Amouyel,P, Anand,S, Blankenberg,S, Boehm,BO, Clarke,RJ, Collins,R, Dedoussis,G, Farrall,M, Franks,PW, Groop,L, Hall,AS, Hamsten,A, Hengstenberg,C, Hovingh,GK, Ingelsson,E, Kathiresan,S, Kee,F, König,IR, Kooner,J, Lehtimäki,T, März,W, McPherson,R, Metspalu,A, Nieminen,MS, O'Donnell,CJ, Palmer,CN, Peters,A, Perola,M, Reilly,MP, Ripatti,S, Roberts,R, Salomaa,V, Shah,SH, Schreiber,S, Siegbahn,A, Thorsteinsdottir,U, Veronesi,G, Wareham,N, Willer,CJ, Zalloua,PA, Erdmann,J, Deloukas,P, Watkins,H, Schunkert,H, Danesh,J, Thompson,JR, Samani,NJ, Assimes,T, Goldstein,BA, Stirrups,K, Cazier,JB, Johansson,Å, Lee,JY, Chambers,JC, Esko,T, Folkersen,L, Goel,A, Grundberg,E, Havulinna,AS, Ho,WK, Eriksson,N, Kleber,ME, Kristiansson,K, Lundmark,P, Lyytikäinen,LP, Rafelt,S, Shungin,D, Strawbridge,RJ, Thorleifsson,G, Tikkanen,E, Van, Zuydam, Voight,BF, Waite,LL, Zhang,W, Ziegler,A, Absher,D, Altshuler,D, Balmforth,AJ, Barroso,I, Braund,PS, Burgdorf,C, Claudi Boehm,S, Cox,D, Dimitriou,M, Do,R, Doney,AS, El, Mokhtari, Eriksson,P, Fischer,K, Fontanillas,P, Franco Cereceda,A, Gigante,B, Gustafsson,S, Hager,J, Hallmans,G, Han,BG, Hunt,SE, Kang,HM, Illig,T, Kessler,T, Knowles,JW, Kolovou,G, Kuusisto,J, Langenberg,C, Langford,C, Leander,K, Lokki,ML, Lundmark,A, McCarthy,MI, Meisinger,C, Melander,O, Mihailov,E, Maouche,S, Morris,AD, Müller Nurasyid,M, Nikus,K, Peden,JF, Rayner,NW, Rasheed,A, Rosinger,S, Rubin,D, Rumpf,MP, Schäfer,A, Sivananthan,M, Song,C, Stewart,AF, Tan,ST, Thorgeirsson,G, van, der, Schoot, CE, Wagner,PJ, Wells,GA, Wild,PS, Yang,TP, Arveiler,D, Basart,H, Boehnke,M, Boerwinkle,E, BRAMBILLA, PAOLO, Cambien,F, Cupples,AL, de, Faire, Dehghan,A, Diemert,P, Epstein,SE, Evans,A, Ferrario,MM, Ferrières,J, Gauguier,D, Go,AS, Goodall,AH, Gudnason,V, Hazen,SL, Holm,H, Iribarren,C, Jang,Y, Kähönen,M, Kim,HS, Klopp,N, Koenig,W, Kratzer,W, Kuulasmaa,K, Laakso,M, Laaksonen,R, Lind,L, Ouwehand,WH, Parish,S, Park,JE, Pedersen,NL, Quertermous,T, Rader,DJ, Schadt,E, Sinisalo,J, Stark,K, Stefansson,K, Trégouët,DA, Virtamo,J, Wallentin,L, Zimmermann,ME, Sandhu,MS, Pastinen,T, Syvänen,AC, Blankenberg,SS, Clarke,R, O'Donnell,C, Kooner,JS, Nelson, C, Hamby, S, Saleheen, D, Hopewell, J, Zeng, L, Assimes, T, Kanoni, S, Willenborg, C, Burgess, S, Amouyel, P, Anand, S, Blankenberg, S, Boehm, B, Clarke, R, Collins, R, Dedoussis, G, Farrall, M, Franks, P, Groop, L, Hall, A, Hamsten, A, Hengstenberg, C, Hovingh, G, Ingelsson, E, Kathiresan, S, Kee, F, König, I, Kooner, J, Lehtimäki, T, März, W, Mcpherson, R, Metspalu, A, Nieminen, M, O'Donnell, C, Palmer, C, Peters, A, Perola, M, Reilly, M, Ripatti, S, Roberts, R, Salomaa, V, Shah, S, Schreiber, S, Siegbahn, A, Thorsteinsdottir, U, Veronesi, G, Wareham, N, Willer, C, Zalloua, P, Erdmann, J, Deloukas, P, Watkins, H, Schunkert, H, Danesh, J, Thompson, J, Samani, N, Goldstein, B, Stirrups, K, Cazier, J, Johansson, Å, Lee, J, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van, Z, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El, M, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, G, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, Van, D, Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, De, F, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Quertermous, T, Rader, D, Schadt, E, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Sandhu, M, Pastinen, T, Syvänen, A, Nelson,CP, Hamby,SE, Saleheen,D, Hopewell,JC, Zeng,L, Assimes,TL, Kanoni,S, Willenborg,C, Burgess,S, Amouyel,P, Anand,S, Blankenberg,S, Boehm,BO, Clarke,RJ, Collins,R, Dedoussis,G, Farrall,M, Franks,PW, Groop,L, Hall,AS, Hamsten,A, Hengstenberg,C, Hovingh,GK, Ingelsson,E, Kathiresan,S, Kee,F, König,IR, Kooner,J, Lehtimäki,T, März,W, McPherson,R, Metspalu,A, Nieminen,MS, O'Donnell,CJ, Palmer,CN, Peters,A, Perola,M, Reilly,MP, Ripatti,S, Roberts,R, Salomaa,V, Shah,SH, Schreiber,S, Siegbahn,A, Thorsteinsdottir,U, Veronesi,G, Wareham,N, Willer,CJ, Zalloua,PA, Erdmann,J, Deloukas,P, Watkins,H, Schunkert,H, Danesh,J, Thompson,JR, Samani,NJ, Assimes,T, Goldstein,BA, Stirrups,K, Cazier,JB, Johansson,Å, Lee,JY, Chambers,JC, Esko,T, Folkersen,L, Goel,A, Grundberg,E, Havulinna,AS, Ho,WK, Eriksson,N, Kleber,ME, Kristiansson,K, Lundmark,P, Lyytikäinen,LP, Rafelt,S, Shungin,D, Strawbridge,RJ, Thorleifsson,G, Tikkanen,E, Van, Zuydam, Voight,BF, Waite,LL, Zhang,W, Ziegler,A, Absher,D, Altshuler,D, Balmforth,AJ, Barroso,I, Braund,PS, Burgdorf,C, Claudi Boehm,S, Cox,D, Dimitriou,M, Do,R, Doney,AS, El, Mokhtari, Eriksson,P, Fischer,K, Fontanillas,P, Franco Cereceda,A, Gigante,B, Gustafsson,S, Hager,J, Hallmans,G, Han,BG, Hunt,SE, Kang,HM, Illig,T, Kessler,T, Knowles,JW, Kolovou,G, Kuusisto,J, Langenberg,C, Langford,C, Leander,K, Lokki,ML, Lundmark,A, McCarthy,MI, Meisinger,C, Melander,O, Mihailov,E, Maouche,S, Morris,AD, Müller Nurasyid,M, Nikus,K, Peden,JF, Rayner,NW, Rasheed,A, Rosinger,S, Rubin,D, Rumpf,MP, Schäfer,A, Sivananthan,M, Song,C, Stewart,AF, Tan,ST, Thorgeirsson,G, van, der, Schoot, CE, Wagner,PJ, Wells,GA, Wild,PS, Yang,TP, Arveiler,D, Basart,H, Boehnke,M, Boerwinkle,E, BRAMBILLA, PAOLO, Cambien,F, Cupples,AL, de, Faire, Dehghan,A, Diemert,P, Epstein,SE, Evans,A, Ferrario,MM, Ferrières,J, Gauguier,D, Go,AS, Goodall,AH, Gudnason,V, Hazen,SL, Holm,H, Iribarren,C, Jang,Y, Kähönen,M, Kim,HS, Klopp,N, Koenig,W, Kratzer,W, Kuulasmaa,K, Laakso,M, Laaksonen,R, Lind,L, Ouwehand,WH, Parish,S, Park,JE, Pedersen,NL, Quertermous,T, Rader,DJ, Schadt,E, Sinisalo,J, Stark,K, Stefansson,K, Trégouët,DA, Virtamo,J, Wallentin,L, Zimmermann,ME, Sandhu,MS, Pastinen,T, Syvänen,AC, Blankenberg,SS, Clarke,R, O'Donnell,C, and Kooner,JS
Abstract: BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.)
Published: 2015

24. Directional dominance on stature and cognition in diverse human populations

Author: Joshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AV, Zhang, WH, Okada, Y, Stancakova, A, Faul, JD, Zhao, W, Bartz, TM, Concas, MP, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, XQ, Chasman, DI, O'Connel, JR, Corre, T, Nongmaithem, SS, Chen, Y, Mangino, M, Ruggiero, D, Michela, T, Farmaki, AE, Kacprowski, T, Bjonnes, A, van der Spek, Ashley, Wu, Y, Giri, AK, Yanek, LR, Wang, LH, Hofer, E, Rietveld, CA, McLeod, O, Cornelis, MC, Pattaro, C, Verweij, N, Baumbach, C, Abdellaoui, A, Warren, HR, Vuckovic, D, Mei, H, Bouchard, C, Perry, JRB, Cappellani, S, Mirza, Saira, Benton, MC, Broeckel, U, Medland, SE, Lind, P, Malerba, G, Drong, A, Yengo, L, Bielak, LF, Zhi, DG, van der Most, PJ, Shriner, D, Magi, R, Hemani, G, Karaderi, T, Wang, ZM, Liu, T, Demuth, I, Zhao, JH, Meng, WH, Lataniotis, L, Laan, Sander, Bradfield, JP, Wood, AR, Bonnefond, A, Ahluwalia, TS, Hall, L, Salvi, E, Yazar, S, Carstensen, L, de Haan, HG, Abney, M, Afzal, U, Allison, MA, Amin, Najaf, Asselbergs, FW, Bakker, SJL, Barr, RG, Baumeister, SE, Benjamin, DJ, Bergmann, S, Boerwinkle, E, Bottinger, EP, Campbell, A (Archie), Chakravarti, A, Chan, YL, Chanock, SJ, Chen, C (Christopher Li Hsian), Chen, YDI, Collins, FS, Connell, J, Correa, A, Cupples, LA, Smith, GD, Davies, G, Dorr, M, Ehret, G, Ellis, SB, Feenstra, B, Feitosa, MF, Ford, I, Fox, CS, Frayling, TM, Friedrich, N, Geller, F, Scotland, G, Gillham-Nasenya, I, Gottesman, O, Graff, M, Grodstein, F, Gu, C, Haley, C, Hammond, CJ, Harris, SE, Harris, TB, Hastie, ND, Heard-Costa, NL, Heikkila, K, Hocking, LJ, Homuth, G, Hottenga, Jouke-Jan, Huang, JY, Huffman, JE, Hysi, Pirro G., Arfan Ikram, M., Ingelsson, E, Joensuu, A, Johansson, A, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kanoni, S, Kerr, SM, Khan, NM, Koellinger, P, Koistinen, HA, Kooner, MK, Kubo, M, Kuusisto, J, Lahti, J, Launer, Lenore J., Lea, RA, Lehne, B, Lehtimaki, T, Liewald, DCM, Lind, L, Loh, M, Lokki, ML, London, SJ, Loomis, SJ, Loukola, A, Lu, YC, Lumley, T, Lundqvist, A, Mannisto, S, Marques-Vidal, P, Masciullo, C, Matchan, A, Mathias, RA, Matsuda, K, Meigs, JB, Meisinger, C, Meitinger, T, Menni, C, Mentch, FD, Mihailov, E, Milani, L, Montasser, ME, Montgomery, G, Morrison, A, Myers, RH, Nadukuru, R, Navarro, P, Nelis, M, Nieminen, MS, Nolte, Ilja M., O'Connor, GT, Ogunniyi, A, Padmanabhan, S, Palmas, WR, Pankow, JS, Patarcic, I, Pavani, F, Peyser, PA, Pietilainen, K, Poulter, N, Prokopenko, I, Ralhan, S, Redmond, P, Rich, SS, Rissanen, H, Robino, A, Rose, LM, Rose, R, Sala, C, Salako, B, Salomaa, V, Sarin, AP, Saxena, R, Schmidt, Heléna, Scott, LJ, Scott, WR, Sennblad, B, Seshadri, S, Sever, P, Shrestha, S, Smith, BH, Smith, JA, Soranzo, N, Sotoodehnia, N, Southam, L, Stanton, AV, Stathopoulou, MG, Strauch, K, Strawbridge, RJ, Suderman, MJ, Tandon, N, Tang, ST, Taylor, KD, Tayo, BO, Toglhofer, AM, Tomaszewski, M, Tsernikova, N, Tuomilehto, J, Uitterlinden, André, Vaidya, D, Vlieg, AV, van Setten, J, Vasankari, T, Vedantam, S, Vlachopoulou, E, Vozzi, D, Vuoksimaa, E, Waldenberger, M, Ware, EB, Wentworth-Shields, W, Whitfield, JB, Wild, S, Willemsen, G, Yajnik, CS, Yao, J, Zaza, G, Zhu, XF, Salem, RM, Melbye, M, Bisgaard, H, Samani, NJ, Cusi, D, Mackey, DA, Cooper, RS, Froguel, P, Pasterkamp, G, Grant, SFA, Hakonarson, H, Ferrucci, L, Scott, RA, Morris, AD, Palmer, CNA, Dedoussis, G, Deloukas, P, Bertram, L, Lindenberger, U, Berndt, SI, Lindgren, CM, Timpson, NJ, Tonjes, A, Munroe, PB, Sorensen, TIA, Rotimi, CN, Arnett, DK, Oldehinkel, Albertine J., Kardia, SLR, Balkau, B, Gambaro, G, Morris, AP, Eriksson, JG, Wright, MJ, Martin, NG, Hunt, SC, Starr, JM, Deary, IJ, Griffiths, LR, Tiemeier, Henning, Pirastu, N, Kaprio, J, Wareham, NJ, Peerusse, L, Wilson, JG, Girotto, G, Caulfield, MJ, Raitakari, O, Boomsma, DI, Gieger, C, van der Harst, P, Hicks, AA, Kraft, P, Sinisalo, J, Knekt, P, Johannesson, M, Magnusson, PKE, Hamsten, A, Schmidt, R, Borecki, IB, Vartiainen, E, Becker, DM, Bharadwaj, D, Mohlke, KL, Boehnke, M, van Duijn, Cornelia M., Sanghera, DK, Teumer, A, Zeggini, E, Metspalu, A, Gasparini, P, Ulivi, S, Ober, C, Toniolo, D, Rudan, I, Porteous, DJ, Ciullo, M, Spector, Tim D., Hayward, C, Dupuis, J, Loos, RJF, Wright, AF, Chandak, GR, Vollenweider, P, Shuldiner, AR, Ridker, PM, Rotter, JI, Sattar, N, Gyllensten, U, North, KE, Pirastu, M, Psaty, Bruce M., Weir, DR, Laakso, M, Gudnason, V, Takahashi, A, Chambers, JC, Kooner, JS, Strachan, DP, Campbell, H, Hirschhorn, JN, Perola, M, Polasek, O, Wilson, JF, Joshi, PK, Esko, T, Mattsson, H, Eklund, N, Gandin, I, Nutile, T, Jackson, AU, Schurmann, C, Smith, AV, Zhang, WH, Okada, Y, Stancakova, A, Faul, JD, Zhao, W, Bartz, TM, Concas, MP, Franceschini, N, Enroth, S, Vitart, V, Trompet, S, Guo, XQ, Chasman, DI, O'Connel, JR, Corre, T, Nongmaithem, SS, Chen, Y, Mangino, M, Ruggiero, D, Michela, T, Farmaki, AE, Kacprowski, T, Bjonnes, A, van der Spek, Ashley, Wu, Y, Giri, AK, Yanek, LR, Wang, LH, Hofer, E, Rietveld, CA, McLeod, O, Cornelis, MC, Pattaro, C, Verweij, N, Baumbach, C, Abdellaoui, A, Warren, HR, Vuckovic, D, Mei, H, Bouchard, C, Perry, JRB, Cappellani, S, Mirza, Saira, Benton, MC, Broeckel, U, Medland, SE, Lind, P, Malerba, G, Drong, A, Yengo, L, Bielak, LF, Zhi, DG, van der Most, PJ, Shriner, D, Magi, R, Hemani, G, Karaderi, T, Wang, ZM, Liu, T, Demuth, I, Zhao, JH, Meng, WH, Lataniotis, L, Laan, Sander, Bradfield, JP, Wood, AR, Bonnefond, A, Ahluwalia, TS, Hall, L, Salvi, E, Yazar, S, Carstensen, L, de Haan, HG, Abney, M, Afzal, U, Allison, MA, Amin, Najaf, Asselbergs, FW, Bakker, SJL, Barr, RG, Baumeister, SE, Benjamin, DJ, Bergmann, S, Boerwinkle, E, Bottinger, EP, Campbell, A (Archie), Chakravarti, A, Chan, YL, Chanock, SJ, Chen, C (Christopher Li Hsian), Chen, YDI, Collins, FS, Connell, J, Correa, A, Cupples, LA, Smith, GD, Davies, G, Dorr, M, Ehret, G, Ellis, SB, Feenstra, B, Feitosa, MF, Ford, I, Fox, CS, Frayling, TM, Friedrich, N, Geller, F, Scotland, G, Gillham-Nasenya, I, Gottesman, O, Graff, M, Grodstein, F, Gu, C, Haley, C, Hammond, CJ, Harris, SE, Harris, TB, Hastie, ND, Heard-Costa, NL, Heikkila, K, Hocking, LJ, Homuth, G, Hottenga, Jouke-Jan, Huang, JY, Huffman, JE, Hysi, Pirro G., Arfan Ikram, M., Ingelsson, E, Joensuu, A, Johansson, A, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kanoni, S, Kerr, SM, Khan, NM, Koellinger, P, Koistinen, HA, Kooner, MK, Kubo, M, Kuusisto, J, Lahti, J, Launer, Lenore J., Lea, RA, Lehne, B, Lehtimaki, T, Liewald, DCM, Lind, L, Loh, M, Lokki, ML, London, SJ, Loomis, SJ, Loukola, A, Lu, YC, Lumley, T, Lundqvist, A, Mannisto, S, Marques-Vidal, P, Masciullo, C, Matchan, A, Mathias, RA, Matsuda, K, Meigs, JB, Meisinger, C, Meitinger, T, Menni, C, Mentch, FD, Mihailov, E, Milani, L, Montasser, ME, Montgomery, G, Morrison, A, Myers, RH, Nadukuru, R, Navarro, P, Nelis, M, Nieminen, MS, Nolte, Ilja M., O'Connor, GT, Ogunniyi, A, Padmanabhan, S, Palmas, WR, Pankow, JS, Patarcic, I, Pavani, F, Peyser, PA, Pietilainen, K, Poulter, N, Prokopenko, I, Ralhan, S, Redmond, P, Rich, SS, Rissanen, H, Robino, A, Rose, LM, Rose, R, Sala, C, Salako, B, Salomaa, V, Sarin, AP, Saxena, R, Schmidt, Heléna, Scott, LJ, Scott, WR, Sennblad, B, Seshadri, S, Sever, P, Shrestha, S, Smith, BH, Smith, JA, Soranzo, N, Sotoodehnia, N, Southam, L, Stanton, AV, Stathopoulou, MG, Strauch, K, Strawbridge, RJ, Suderman, MJ, Tandon, N, Tang, ST, Taylor, KD, Tayo, BO, Toglhofer, AM, Tomaszewski, M, Tsernikova, N, Tuomilehto, J, Uitterlinden, André, Vaidya, D, Vlieg, AV, van Setten, J, Vasankari, T, Vedantam, S, Vlachopoulou, E, Vozzi, D, Vuoksimaa, E, Waldenberger, M, Ware, EB, Wentworth-Shields, W, Whitfield, JB, Wild, S, Willemsen, G, Yajnik, CS, Yao, J, Zaza, G, Zhu, XF, Salem, RM, Melbye, M, Bisgaard, H, Samani, NJ, Cusi, D, Mackey, DA, Cooper, RS, Froguel, P, Pasterkamp, G, Grant, SFA, Hakonarson, H, Ferrucci, L, Scott, RA, Morris, AD, Palmer, CNA, Dedoussis, G, Deloukas, P, Bertram, L, Lindenberger, U, Berndt, SI, Lindgren, CM, Timpson, NJ, Tonjes, A, Munroe, PB, Sorensen, TIA, Rotimi, CN, Arnett, DK, Oldehinkel, Albertine J., Kardia, SLR, Balkau, B, Gambaro, G, Morris, AP, Eriksson, JG, Wright, MJ, Martin, NG, Hunt, SC, Starr, JM, Deary, IJ, Griffiths, LR, Tiemeier, Henning, Pirastu, N, Kaprio, J, Wareham, NJ, Peerusse, L, Wilson, JG, Girotto, G, Caulfield, MJ, Raitakari, O, Boomsma, DI, Gieger, C, van der Harst, P, Hicks, AA, Kraft, P, Sinisalo, J, Knekt, P, Johannesson, M, Magnusson, PKE, Hamsten, A, Schmidt, R, Borecki, IB, Vartiainen, E, Becker, DM, Bharadwaj, D, Mohlke, KL, Boehnke, M, van Duijn, Cornelia M., Sanghera, DK, Teumer, A, Zeggini, E, Metspalu, A, Gasparini, P, Ulivi, S, Ober, C, Toniolo, D, Rudan, I, Porteous, DJ, Ciullo, M, Spector, Tim D., Hayward, C, Dupuis, J, Loos, RJF, Wright, AF, Chandak, GR, Vollenweider, P, Shuldiner, AR, Ridker, PM, Rotter, JI, Sattar, N, Gyllensten, U, North, KE, Pirastu, M, Psaty, Bruce M., Weir, DR, Laakso, M, Gudnason, V, Takahashi, A, Chambers, JC, Kooner, JS, Strachan, DP, Campbell, H, Hirschhorn, JN, Perola, M, Polasek, O, and Wilson, JF
Abstract: Homozygosity has long been associated with rare, often devastating, Mendelian disorders(1), and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness(2). However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power(3,4). Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 x 10(-300), 2.1 x 10(-6), 2.5 x 10(-10) and 1.8 x 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples(5,6), no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection(7), this study provides evidence that increased stature and cognitive function have been positively sele
Published: 2015

25. Clinical impact of 'in-treatment' wall motion abnormalities in hypertensive atients with left ventricular hypertrophy: the LIFE Study

Author: Cicala S, Wachtel K, Gerdts E, Boman K, Nieminen MS, Dahlöf B, Devereux RB, DE SIMONE, GIOVANNI, Cicala, S, DE SIMONE, Giovanni, Wachtel, K, Gerdts, E, Boman, K, Nieminen, M, Dahlöf, B, and Devereux, Rb
Published: 2008

26. Guidelines for the Diagnosis and Treatment of Chronic Heart Failure

Author: Swedberg, Karl, Cleland, J, Dargie, H, Drexler, H, Follath, F, Komajda, M, Tavazzi, L, Smiseth, OA, Gavazzi, A, Haverich, A, Hoes, A, Jaarsma, T, Korewicki, J, Levy, S, Linde, C, Lopez-Sendon, JL, Nieminen, MS, Pierard, L, and Remme, WJ
Subjects: business.industry, CONVERTING-ENZYME-INHIBITORS, RANDOMIZED CONTROLLED-TRIALS, IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR, ACUTE CORONARY SYNDROMES, ANTIARRHYTHMIC-DRUG-THERAPY, LEFT-VENTRICULAR DYSFUNCTION, EXERCISE OXYGEN-CONSUMPTION, BRAIN NATRIURETIC PEPTIDE, CARDIOVASCULAR MAGNETIC-RESONANCE, Medicine, HOME-BASED INTERVENTION, Cardiology and Cardiovascular Medicine, business, Humanities
Published: 2005

27. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology

Author: NIEMINEN MS., BOHM M., COWIE M., DREXLER H., FILIPPATOS G., JONDEAU G., HASIN Y., LOPEZSENDON J., MEBAZAA A., METRA M., RHODES A., SWEDBERG K., PRIORI S., GARCIA M., BLANC J., BUDAJ A., DEAN V., DECKERS J., BURGOS E., LEKAKIS J., LINDAHL B., MAZZOTTA G., MORAIS J., OTO A., SMISETH O., DICKSTEIN K., ALBUQUERQUE A., CONTHE P., CRESPO‐LEIRO M., FERRARI R., FOLLATH F., GAVAZZI A., JANSSENS U., KOMAJDA M., MORENO R., SINGER M., SINGH S., TENDERA M., THYGESEN K., and ESC COMMITTE FOR PRACTICE GUIDELINE (CPG)
Abstract: We found 1 article: Eur Heart J. 2005 Feb;26(4):384-416. Epub 2005 Jan 28. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology. Nieminen MS, Böhm M, Cowie MR, Drexler H, Filippatos GS, Jondeau G, Hasin Y, Lopez-Sendon J, Mebazaa A, Metra M, Rhodes A, Swedberg K, Priori SG, Garcia MA, Blanc JJ, Budaj A, Cowie MR, Dean V, Deckers J, Burgos EF, Lekakis J, Lindahl B, Mazzotta G, Morais J, Oto A, Smiseth OA, Garcia MA, Dickstein K, Albuquerque A, Conthe P, Crespo-Leiro M, Ferrari R, Follath F, Gavazzi A, Janssens U, Komajda M, Morais J, Moreno R, Singer M, Singh S, Tendera M, Thygesen K; ESC Committe for Practice Guideline (CPG). Division of Cardiology, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland. markku.nieminen@hus.fi PMID: 15681577 [PubMed - indexed for MEDLINE]Free Article
Published: 2005

28. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005)

Author: Swedberg, K, Cleland, J, Dargie, H, Drexler, H, Follath, F, Komajda, M, Tavazzi, L, Smiseth, Oa, Gavazzi, A, Haverich, A, Hoes, A, Jaarsma, T, Korewicki, J, Levy, S, Linde, C, LOPEZ SENDON JL, Nieminen, Ms, Pierard, L, Priori, REMME W. J., Blanc, J. J., Budaj, A, Camm, J, Dean, V, Deckers, J, Dickstein, K, Lekakis, J, Mcgregor, K, Morais, J, Osterpey, A, Tamargo, J, Zamorano, Jl, Metra, Marco, Bohm, M, COHE SOLAL, A, Cowie, M, Dahlstrom, U, Filippatos, Gs, Gronda, E, Hobbs, R, Kjekshus, Jk, Mcmurray, J, Ryden, L, Sinagra, G, Tendera, M, VAN VELDHUISEN, D, and Zannad, F.
Published: 2005

29. Body Build and Risk of Cardiovascular Events in Hypertension and Left Ventricular Hypertrophy. The LIFE Study

Author: DE SIMONE, GIOVANNI, PALMIERI, VITTORIO, WACHTEL K, HILLE DA, BEEVERS G, DAHLOF B, DE FAIRE U, FYHRQUIST F, IBSEN H, JULIUS S, KJELDSEN S, LEDERBALLE PEDERSEN O, LINDHOLM LH, NIEMINEN MS, OMVIK P, OPARIL S, DEVEREUX R.B., DE SIMONE, Giovanni, Wachtel, K, Palmieri, Vittorio, Hille, Da, Beevers, G, Dahlof, B, DE FAIRE, U, Fyhrquist, F, Ibsen, H, Julius, S, Kjeldsen, S, LEDERBALLE PEDERSEN, O, Lindholm, Lh, Nieminen, M, Omvik, P, Oparil, S, and Devereux, R. B.
Published: 2005

30. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Author: Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., BRAMBILLA, PAOLO, Berndt, S, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, M, Justice, A, Monda, K, Croteau Chonka, D, Day, F, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, A, Luan, J, Randall, J, Vedantam, S, Willer, C, Winkler, T, Wood, A, Workalemahu, T, Hu, Y, Lee, S, Liang, L, Lin, D, Min, J, Neale, B, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg Gresham, J, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J, Huffman, J, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, M, König, I, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, Mcardle, W, Medina Gomez, C, Müller Nurasyid, M, Ngwa, J, Nolte, I, Paternoster, L, Pechlivanis, S, Perola, M, Peters, M, Preuss, M, Rose, L, Shi, J, Shungin, D, Smith, A, Strawbridge, R, Surakka, I, Teumer, A, Trip, M, Tyrer, J, Van Vliet Ostaptchouk, J, Vandenput, L, Waite, L, Zhao, J, Absher, D, Asselbergs, F, Atalay, M, Attwood, A, Balmforth, A, Basart, H, Beilby, J, Bonnycastle, L, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, D, Chines, P, Collins, F, Connell, J, Cookson, W, De, F, U, D, Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, D, Farrall, M, Ferrario, M, Ferrières, J, Franke, L, Frau, F, Gejman, P, Grallert, H, Grönberg, H, Gudnason, V, Hall, A, Hall, P, Hartikainen, A, Hayward, C, Heard Costa, N, Heath, A, Hebebrand, J, Homuth, G, Hu, F, Hunt, S, Hyppönen, E, Iribarren, C, Jacobs, K, Jansson, J, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K, Kivimäki, M, Koenig, W, Kraja, A, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, J, Lakka, T, Langenberg, C, Launer, L, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M, Lorentzon, M, Madden, P, Magnusson, P, Manunta, P, Marek, D, März, W, Mateo Leach, I, Mcknight, B, Medland, S, Mihailov, E, Milani, L, Montgomery, G, Mooser, V, Mühleisen, T, Munroe, P, Musk, A, Narisu, N, Navis, G, Nicholson, G, Nohr, E, Ong, K, Oostra, B, Palmer, C, Palotie, A, Peden, J, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, P, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, T, Sambrook, J, Sanders, A, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stančáková, A, Stark, K, Stephens, J, Stirrups, K, Stolk, R, Stumvoll, M, Swift, A, Theodoraki, E, Thorand, B, Tregouet, D, Tremoli, E, Van der Klauw, M, van Meurs, J, Vermeulen, S, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, S, Willemsen, G, Winkelmann, B, Witteman, J, Wolffenbuttel, B, Wong, A, Wright, A, Zillikens, M, Amouyel, P, Boehm, B, Boerwinkle, E, Boomsma, D, Caulfield, M, Chanock, S, Cupples, L, Cusi, D, Dedoussis, G, Erdmann, J, Eriksson, J, Franks, P, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, T, Hengstenberg, C, Hicks, A, Hingorani, A, Hinney, A, Hofman, A, Hovingh, K, Hveem, K, Illig, T, Jarvelin, M, Jöckel, K, Keinanen Kiukaanniemi, S, Kiemeney, L, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, D, Martin, N, Metspalu, A, Morris, A, Nieminen, M, Njølstad, I, Ohlsson, C, Oldehinkel, A, Ouwehand, W, Palmer, L, Penninx, B, Power, C, Province, M, Psaty, B, Qi, L, Rauramaa, R, Ridker, P, Ripatti, S, Salomaa, V, Samani, N, Snieder, H, Sørensen, T, Spector, T, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Abecasis, G, Assimes, T, Barroso, I, Boehnke, M, Borecki, I, Deloukas, P, Fox, C, Frayling, T, Groop, L, Haritunian, T, Heid, I, Hunter, D, Kaplan, R, Karpe, F, Moffatt, M, Mohlke, K, O'Connell, J, Pawitan, Y, Schadt, E, Schlessinger, D, Steinthorsdottir, V, Strachan, D, Thorsteinsdottir, U, Van, D, Cm, Visscher, P, Di Blasio, A, Hirschhorn, J, Lindgren, C, Meyre, D, Scherag, A, Mccarthy, M, Speliotes, E, North, K, Loos, R, Ingelsson, E, Berndt, SI, Feitosa, MF, Justice, AE, Monda, KL, Croteau Chonka, DC, Day, FR, Jackson, AU, Randall, JC, Willer, CJ, Winkler, TW, Wood, AR, Hu, YJ, Lee, SH, Lin, DY, Min, JL, Neale, BM, Bragg Gresham, JL, Hottenga, JJ, Huffman, JE, Kleber, ME, König, IR, McArdle, WL, Ngwa, JS, Nolte, IM, Peters, MJ, Rose, LM, Smith, AV, Strawbridge, RJ, Trip, MD, Van Vliet Ostaptchouk, JV, Waite, LL, Zhao, JH, Asselbergs, FW, Attwood, AP, Balmforth, AJ, Bonnycastle, LL, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de, Faire, U, de, Evans, DM, Ferrario, MM, Gejman, PV, Hall, AS, Hartikainen, AL, Heard Costa, NL, Heath, AC, Hu, FB, Hunt, SE, Jacobs, KB, Jansson, JO, Khaw, KT, Kraja, AT, Laitinen, JH, Lakka, TA, Launer, LJ, Lokki, ML, Madden, PA, Magnusson, PK, McKnight, B, Medland, SE, Montgomery, GW, Mühleisen, TW, Munroe, PB, Musk, AW, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CN, Peden, JF, Pramstaller, PP, Saaristo, TE, Sambrook, JG, Sanders, AR, Shin, SY, Stephens, JC, Stolk, RP, Swift, AJ, Theodoraki, EV, Tregouet, DA, Van der Klauw, MM, van Meurs, JB, Vermeulen, SH, Wild, SH, Winkelmann, BR, Witteman, JC, Wolffenbuttel, BH, Wright, AF, Zillikens, MC, Boehm, BO, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Dedoussis, GV, Eriksson, JG, Franks, PW, Harris, TB, Hicks, AA, Hovingh, KG, Jarvelin, MR, Jöckel, KH, Keinanen Kiukaanniemi, SM, Kiemeney, LA, Levinson, DF, Martin, NG, Morris, AD, Nieminen, MS, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Province, MA, Psaty, BM, Ridker, PM, Samani, NJ, Sørensen, TI, Spector, TD, Uitterlinden, AG, Wareham, NJ, Wichmann, HE, Wilson, JF, Abecasis, GR, Assimes, TL, Borecki, IB, Fox, CS, Groop, LC, Heid, IM, Kaplan, RC, Moffatt, MF, Mohlke, KL, O'Connell, JR, Schadt, EE, Strachan, DP, van, Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJ, Ingelsson, E., and BRAMBILLA, PAOLO
Abstract: Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups
Published: 2013

31. Large-scale association analysis identifies new risk loci for coronary artery disease

Author: Deloukas, P, Kanoni, S, Willenborg, C, Farrall, M, Assimes, T, Thompson, J, Ingelsson, E, Saleheen, D, Erdmann, J, Goldstein, B, Stirrups, K, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Willer, C, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van Zuydam, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El Mokhtari, N, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Groop, L, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, J, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Amouyel, P, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kee, F, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Peters, A, Quertermous, T, Rader, D, Salomaa, V, Schadt, E, Shah, S, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Wareham, N, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Syvänen, A, Hovingh, G, Dedoussis, G, Franks, P, Lehtimäki, T, Metspalu, A, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, Perola, M, Clarke, R, Boehm, B, O’Donnell, C, Reilly, M, März, W, Collins, R, Kathiresan, S, Hamsten, A, Kooner, J, Thorsteinsdottir, U, Danesh, J, Palmer, C, Roberts, R, Watkins, H, Schunkert, H, Samani, N, Assimes, TL, Thompson, JR, Goldstein, BA, König, IR, Cazier, JB, Hall, AS, Lee, JY, Willer, CJ, Chambers, JC, Havulinna, AS, Ho, WK, Hopewell, JC, Kleber, ME, Lyytikäinen, LP, Strawbridge, RJ, Voight, BF, Waite, LL, Balmforth, AJ, Braund, PS, Doney, ASF, El Mokhtari, NE, Han, BG, Hunt, SE, Kang, HM, Knowles, JW, Lokki, ML, McCarthy, MI, Morris, AD, Peden, JF, Rayner, NW, Rumpf, MP, Stewart, AFR, Tan, S. T, van der Schoot, CE, Wagner, PJ, Wells, GA, Wild, PS, Yang, T. P, Cupples, AL, Epstein, SE, Ferrario, MM, Go, AS, Goodall, AH, Hazen, SL, Kim, H. S, Lee, J. Y, Ouwehand, WH, Park, JE, Pedersen, NL, Rader, DJ, Shah, SH, Trégouët, D. A, Zimmermann, ME, Nieminen, MS, Sandhu, MS, Syvänen, A. C, Hovingh, GK, Franks, PW, Zalloua, PA, Blankenberg, SS, Boehm, BO, Reilly, MP, Kooner, JS, Palmer, CNA, Samani, NJ, BRAMBILLA, PAOLO, Deloukas, P, Kanoni, S, Willenborg, C, Farrall, M, Assimes, T, Thompson, J, Ingelsson, E, Saleheen, D, Erdmann, J, Goldstein, B, Stirrups, K, König, I, Cazier, J, Johansson, Å, Hall, A, Lee, J, Willer, C, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van Zuydam, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El Mokhtari, N, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Groop, L, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, J, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Amouyel, P, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, de Faire, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kee, F, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Peters, A, Quertermous, T, Rader, D, Salomaa, V, Schadt, E, Shah, S, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Wareham, N, Zimmermann, M, Nieminen, M, Hengstenberg, C, Sandhu, M, Pastinen, T, Syvänen, A, Hovingh, G, Dedoussis, G, Franks, P, Lehtimäki, T, Metspalu, A, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, Perola, M, Clarke, R, Boehm, B, O’Donnell, C, Reilly, M, März, W, Collins, R, Kathiresan, S, Hamsten, A, Kooner, J, Thorsteinsdottir, U, Danesh, J, Palmer, C, Roberts, R, Watkins, H, Schunkert, H, Samani, N, Assimes, TL, Thompson, JR, Goldstein, BA, König, IR, Cazier, JB, Hall, AS, Lee, JY, Willer, CJ, Chambers, JC, Havulinna, AS, Ho, WK, Hopewell, JC, Kleber, ME, Lyytikäinen, LP, Strawbridge, RJ, Voight, BF, Waite, LL, Balmforth, AJ, Braund, PS, Doney, ASF, El Mokhtari, NE, Han, BG, Hunt, SE, Kang, HM, Knowles, JW, Lokki, ML, McCarthy, MI, Morris, AD, Peden, JF, Rayner, NW, Rumpf, MP, Stewart, AFR, Tan, S. T, van der Schoot, CE, Wagner, PJ, Wells, GA, Wild, PS, Yang, T. P, Cupples, AL, Epstein, SE, Ferrario, MM, Go, AS, Goodall, AH, Hazen, SL, Kim, H. S, Lee, J. Y, Ouwehand, WH, Park, JE, Pedersen, NL, Rader, DJ, Shah, SH, Trégouët, D. A, Zimmermann, ME, Nieminen, MS, Sandhu, MS, Syvänen, A. C, Hovingh, GK, Franks, PW, Zalloua, PA, Blankenberg, SS, Boehm, BO, Reilly, MP, Kooner, JS, Palmer, CNA, Samani, NJ, and BRAMBILLA, PAOLO
Abstract: Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways
Published: 2013

32. Genome-wide meta-analysis of common variant differences between men and women

Author: Boraska, V, Jeroncic, A, Colonna, V, Southam, L, Nyholt, DR, Rayner, NW, Perry, JRB, Toniolo, D, Albrecht, E, Ang, W, Bandinelli, S, Barbalic, M, Barroso, I, Beckmann, JS, Biffar, R, Boomsma, D, Campbell, H, Corre, T, Erdmann, J, Esko, T, Fischer, K (Kirsten), Franceschini, N, Frayling, TM, Girotto, G, Gonzalez, JR, Harris, TB, Heath, AC, Heid, IM, Hoffmann, W, Hofman, Bert, Horikoshi, M, Zhao, JH, Jackson, AU, Hottenga, JJ (Jouke Jan), Jula, A, Kahonen, M, Khaw, KT, Kiemeney, LA, Klopp, N, Kutalik, Z, Lagou, V, Launer, LJ (Lenore), Lehtimaki, T, Lemire, M, Lokki, ML, Loley, C, Luan, JA, Mangino, M, Leach, IM, Medland, SE, Mihailov, E, Montgomery, GW, Navis, G, Newnham, J, Nieminen, MS, Palotie, A, Panoutsopoulou, K, Peters, A, Pirastu, N, Polasek, O, Rehnstrom, K, Ripatti, S, Ritchie, GRS, Rivadeneira, Fernando, Robino, A, Samani, NJ, Shin, SY, Sinisalo, J, Smit, JH, Soranzo, N, Stolk, Lisette, Swinkels, DW, Tanaka, T, Teumer, A, Tonjes, A, Traglia, M, Tuomilehto, J, Valsesia, A, van Gilst, WH, van Meurs, Joyce, Smith, AV, Viikari, J, Vink, JM, Waeber, G, Warrington, NM, Widen, E, Willemsen, G, Wright, AF, Zanke, BW, Zgaga, L, Boehnke, M, d'Adamo, AP, de Geus, ED, Demerath, EW, Heijer, Mariska, Eriksson, JG, Ferrucci, L, Gieger, C, Gudnason, V, Hayward, C, Hengstenberg, C, Hudson, TJ, Jarvelin, MR, Kogevinas, M, Loos, RJF, Martin, NG, Metspalu, A, Pennell, CE, Penninx, BW, Perola, M, Raitakari, O, Salomaa, V, Schreiber, S, Schunkert, H, Spector, TD, Stumvoll, M, Uitterlinden, André, Ulivi, S, van der Harst, P, Vollenweider, P, Volzke, H, Wareham, NJ, Wichmann, HE, Wilson, JF, Rudan, I, Xue, YL, Zeggini, E, Boraska, V, Jeroncic, A, Colonna, V, Southam, L, Nyholt, DR, Rayner, NW, Perry, JRB, Toniolo, D, Albrecht, E, Ang, W, Bandinelli, S, Barbalic, M, Barroso, I, Beckmann, JS, Biffar, R, Boomsma, D, Campbell, H, Corre, T, Erdmann, J, Esko, T, Fischer, K (Kirsten), Franceschini, N, Frayling, TM, Girotto, G, Gonzalez, JR, Harris, TB, Heath, AC, Heid, IM, Hoffmann, W, Hofman, Bert, Horikoshi, M, Zhao, JH, Jackson, AU, Hottenga, JJ (Jouke Jan), Jula, A, Kahonen, M, Khaw, KT, Kiemeney, LA, Klopp, N, Kutalik, Z, Lagou, V, Launer, LJ (Lenore), Lehtimaki, T, Lemire, M, Lokki, ML, Loley, C, Luan, JA, Mangino, M, Leach, IM, Medland, SE, Mihailov, E, Montgomery, GW, Navis, G, Newnham, J, Nieminen, MS, Palotie, A, Panoutsopoulou, K, Peters, A, Pirastu, N, Polasek, O, Rehnstrom, K, Ripatti, S, Ritchie, GRS, Rivadeneira, Fernando, Robino, A, Samani, NJ, Shin, SY, Sinisalo, J, Smit, JH, Soranzo, N, Stolk, Lisette, Swinkels, DW, Tanaka, T, Teumer, A, Tonjes, A, Traglia, M, Tuomilehto, J, Valsesia, A, van Gilst, WH, van Meurs, Joyce, Smith, AV, Viikari, J, Vink, JM, Waeber, G, Warrington, NM, Widen, E, Willemsen, G, Wright, AF, Zanke, BW, Zgaga, L, Boehnke, M, d'Adamo, AP, de Geus, ED, Demerath, EW, Heijer, Mariska, Eriksson, JG, Ferrucci, L, Gieger, C, Gudnason, V, Hayward, C, Hengstenberg, C, Hudson, TJ, Jarvelin, MR, Kogevinas, M, Loos, RJF, Martin, NG, Metspalu, A, Pennell, CE, Penninx, BW, Perola, M, Raitakari, O, Salomaa, V, Schreiber, S, Schunkert, H, Spector, TD, Stumvoll, M, Uitterlinden, André, Ulivi, S, van der Harst, P, Vollenweider, P, Volzke, H, Wareham, NJ, Wichmann, HE, Wilson, JF, Rudan, I, Xue, YL, and Zeggini, E
Abstract: The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency 0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P 5 10(8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across approximate to 115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.
Published: 2012

33. Biological, clinical and population relevance of 95 loci for blood lipids

Author: Teslovich, TM, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, Koseki, M, Pirruccello, JP, Ripatti, S, Chasman, DI, Willer, CJ, Johansen, CT, Fouchier, SW, Isaacs, A, Peloso, GM, Barbalic, M, Ricketts, SL, Bis, JC, Aulchenko, YS, Thorleifsson, G, Feitosa, MF, Chambers, J, Orho-Melander, M, Melander, O, Johnson, T, Li, X, Guo, X, Li, M, Cho, YS, Go, MJ, Kim, YJ, Lee, J-Y, Park, T, Kim, K, Sim, X, Ong, RT-H, Croteau-Chonka, DC, Lange, LA, Smith, JD, Song, K, Zhao, JH, Yuan, X, Luan, J, Lamina, C, Ziegler, A, Zhang, W, Zee, RYL, Wright, AF, Witteman, JCM, Wilson, JF, Willemsen, G, Wichmann, H-E, Whitfield, JB, Waterworth, DM, Wareham, NJ, Waeber, G, Vollenweider, P, Voight, BF, Vitart, V, Uitterlinden, AG, Uda, M, Tuomilehto, J, Thompson, JR, Tanaka, T, Surakka, I, Stringham, HM, Spector, TD, Soranzo, N, Smit, JH, Sinisalo, J, Silander, K, Sijbrands, EJG, Scuteri, A, Scott, J, Schlessinger, D, Sanna, S, Salomaa, V, Saharinen, J, Sabatti, C, Ruokonen, A, Rudan, I, Rose, LM, Roberts, R, Rieder, M, Psaty, BM, Pramstaller, PP, Pichler, I, Perola, M, Penninx, BWJH, Pedersen, NL, Pattaro, C, Parker, AN, Pare, G, Oostra, BA, O'Donnell, CJ, Nieminen, MS, Nickerson, DA, Montgomery, GW, Meitinger, T, McPherson, R, McCarthy, MI, McArdle, W, Masson, D, Martin, NG, Marroni, F, Mangino, M, Magnusson, PKE, Lucas, G, Luben, R, Loos, RJF, Lokki, M-L, Lettre, G, Langenberg, C, Launer, LJ, Lakatta, EG, Laaksonen, R, Kyvik, KO, Kronenberg, F, Koenig, IR, Khaw, K-T, Kaprio, J, Kaplan, LM, Johansson, A, Jarvelin, M-R, Janssens, ACJW, Ingelsson, E, Igi, W, Hovingh, GK, Hottenga, J-J, Hofman, A, Hicks, AA, Hengstenberg, C, Heid, IM, Hayward, C, Havulinna, AS, Hastie, ND, Harris, TB, Haritunians, T, Hall, AS, Gyllensten, U, Guiducci, C, Groop, LC, Gonzalez, E, Gieger, C, Freimer, NB, Ferrucci, L, Erdmann, J, Elliott, P, Ejebe, KG, Doering, A, Dominiczak, AF, Demissie, S, Deloukas, P, de Geus, EJC, de Faire, U, Crawford, G, Collins, FS, Chen, Y-DI, Caulfield, MJ, Campbell, H, Burtt, NP, Bonnycastle, LL, Boomsma, DI, Boekholdt, SM, Bergman, RN, Barroso, I, Bandinelli, S, Ballantyne, CM, Assimes, TL, Quertermous, T, Altshuler, D, Seielstad, M, Wong, TY, Tai, E-S, Feranil, AB, Kuzawa, CW, Adair, LS, Taylor, HA, Borecki, IB, Gabriel, SB, Wilson, JG, Holm, H, Thorsteinsdottir, U, Gudnason, V, Krauss, RM, Mohlke, KL, Ordovas, JM, Munroe, PB, Kooner, JS, Tall, AR, Hegele, RA, Kastelein, JJP, Schadt, EE, Rotter, JI, Boerwinkle, E, Strachan, DP, Mooser, V, Stefansson, K, Reilly, MP, Samani, NJ, Schunkert, H, Cupples, LA, Sandhu, MS, Ridker, PM, Rader, DJ, van Duijn, CM, Peltonen, L, Abecasis, GR, Boehnke, M, Kathiresan, S, Teslovich, TM, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, Koseki, M, Pirruccello, JP, Ripatti, S, Chasman, DI, Willer, CJ, Johansen, CT, Fouchier, SW, Isaacs, A, Peloso, GM, Barbalic, M, Ricketts, SL, Bis, JC, Aulchenko, YS, Thorleifsson, G, Feitosa, MF, Chambers, J, Orho-Melander, M, Melander, O, Johnson, T, Li, X, Guo, X, Li, M, Cho, YS, Go, MJ, Kim, YJ, Lee, J-Y, Park, T, Kim, K, Sim, X, Ong, RT-H, Croteau-Chonka, DC, Lange, LA, Smith, JD, Song, K, Zhao, JH, Yuan, X, Luan, J, Lamina, C, Ziegler, A, Zhang, W, Zee, RYL, Wright, AF, Witteman, JCM, Wilson, JF, Willemsen, G, Wichmann, H-E, Whitfield, JB, Waterworth, DM, Wareham, NJ, Waeber, G, Vollenweider, P, Voight, BF, Vitart, V, Uitterlinden, AG, Uda, M, Tuomilehto, J, Thompson, JR, Tanaka, T, Surakka, I, Stringham, HM, Spector, TD, Soranzo, N, Smit, JH, Sinisalo, J, Silander, K, Sijbrands, EJG, Scuteri, A, Scott, J, Schlessinger, D, Sanna, S, Salomaa, V, Saharinen, J, Sabatti, C, Ruokonen, A, Rudan, I, Rose, LM, Roberts, R, Rieder, M, Psaty, BM, Pramstaller, PP, Pichler, I, Perola, M, Penninx, BWJH, Pedersen, NL, Pattaro, C, Parker, AN, Pare, G, Oostra, BA, O'Donnell, CJ, Nieminen, MS, Nickerson, DA, Montgomery, GW, Meitinger, T, McPherson, R, McCarthy, MI, McArdle, W, Masson, D, Martin, NG, Marroni, F, Mangino, M, Magnusson, PKE, Lucas, G, Luben, R, Loos, RJF, Lokki, M-L, Lettre, G, Langenberg, C, Launer, LJ, Lakatta, EG, Laaksonen, R, Kyvik, KO, Kronenberg, F, Koenig, IR, Khaw, K-T, Kaprio, J, Kaplan, LM, Johansson, A, Jarvelin, M-R, Janssens, ACJW, Ingelsson, E, Igi, W, Hovingh, GK, Hottenga, J-J, Hofman, A, Hicks, AA, Hengstenberg, C, Heid, IM, Hayward, C, Havulinna, AS, Hastie, ND, Harris, TB, Haritunians, T, Hall, AS, Gyllensten, U, Guiducci, C, Groop, LC, Gonzalez, E, Gieger, C, Freimer, NB, Ferrucci, L, Erdmann, J, Elliott, P, Ejebe, KG, Doering, A, Dominiczak, AF, Demissie, S, Deloukas, P, de Geus, EJC, de Faire, U, Crawford, G, Collins, FS, Chen, Y-DI, Caulfield, MJ, Campbell, H, Burtt, NP, Bonnycastle, LL, Boomsma, DI, Boekholdt, SM, Bergman, RN, Barroso, I, Bandinelli, S, Ballantyne, CM, Assimes, TL, Quertermous, T, Altshuler, D, Seielstad, M, Wong, TY, Tai, E-S, Feranil, AB, Kuzawa, CW, Adair, LS, Taylor, HA, Borecki, IB, Gabriel, SB, Wilson, JG, Holm, H, Thorsteinsdottir, U, Gudnason, V, Krauss, RM, Mohlke, KL, Ordovas, JM, Munroe, PB, Kooner, JS, Tall, AR, Hegele, RA, Kastelein, JJP, Schadt, EE, Rotter, JI, Boerwinkle, E, Strachan, DP, Mooser, V, Stefansson, K, Reilly, MP, Samani, NJ, Schunkert, H, Cupples, LA, Sandhu, MS, Ridker, PM, Rader, DJ, van Duijn, CM, Peltonen, L, Abecasis, GR, Boehnke, M, and Kathiresan, S
Abstract: Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
Published: 2010

34. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author: Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, Hirschhorn, JN, Allen, HL, Estrada, K, Lettre, G, Berndt, SI, Weedon, MN, Rivadeneira, F, Willer, CJ, Jackson, AU, Vedantam, S, Raychaudhuri, S, Ferreira, T, Wood, AR, Weyant, RJ, Segre, AV, Speliotes, EK, Wheeler, E, Soranzo, N, Park, J-H, Yang, J, Gudbjartsson, D, Heard-Costa, NL, Randall, JC, Qi, L, Smith, AV, Maegi, R, Pastinen, T, Liang, L, Heid, IM, Luan, J, Thorleifsson, G, Winkler, TW, Goddard, ME, Lo, KS, Palmer, C, Workalemahu, T, Aulchenko, YS, Johansson, A, Zillikens, MC, Feitosa, MF, Esko, T, Johnson, T, Ketkar, S, Kraft, P, Mangino, M, Prokopenko, I, Absher, D, Albrecht, E, Ernst, F, Glazer, NL, Hayward, C, Hottenga, J-J, Jacobs, KB, Knowles, JW, Kutalik, Z, Monda, KL, Polasek, O, Preuss, M, Rayner, NW, Robertson, NR, Steinthorsdottir, V, Tyrer, JP, Voight, BF, Wiklund, F, Xu, J, Zhao, JH, Nyholt, DR, Pellikka, N, Perola, M, Perry, JRB, Surakka, I, Tammesoo, M-L, Altmaier, EL, Amin, N, Aspelund, T, Bhangale, T, Boucher, G, Chasman, DI, Chen, C, Coin, L, Cooper, MN, Dixon, AL, Gibson, Q, Grundberg, E, Hao, K, Junttila, MJ, Kaplan, LM, Kettunen, J, Koenig, IR, Kwan, T, Lawrence, RW, Levinson, DF, Lorentzon, M, McKnight, B, Morris, AP, Mueller, M, Ngwa, JS, Purcell, S, Rafelt, S, Salem, RM, Salvi, E, Sanna, S, Shi, J, Sovio, U, Thompson, JR, Turchin, MC, Vandenput, L, Verlaan, DJ, Vitart, V, White, CC, Ziegler, A, Almgren, P, Balmforth, AJ, Campbell, H, Citterio, L, De Grandi, A, Dominiczak, A, Duan, J, Elliott, P, Elosua, R, Eriksson, JG, Freimer, NB, Geus, EJC, Glorioso, N, Haiqing, S, Hartikainen, A-L, Havulinna, AS, Hicks, AA, Hui, J, Igl, W, Illig, T, Jula, A, Kajantie, E, Kilpelaeinen, TO, Koiranen, M, Kolcic, I, Koskinen, S, Kovacs, P, Laitinen, J, Liu, J, Lokki, M-L, Marusic, A, Maschio, A, Meitinger, T, Mulas, A, Pare, G, Parker, AN, Peden, JF, Petersmann, A, Pichler, I, Pietilainen, KH, Pouta, A, Riddertrale, M, Rotter, JI, Sambrook, JG, Sanders, AR, Schmidt, CO, Sinisalo, J, Smit, JH, Stringham, HM, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Zagato, L, Zgaga, L, Zitting, P, Alavere, H, Farrall, M, McArdle, WL, Nelis, M, Peters, MJ, Ripatti, S, vVan Meurs, JBJ, Aben, KK, Ardlie, KG, Beckmann, JS, Beilby, JP, Bergman, RN, Bergmann, S, Collins, FS, Cusi, D, den Heijer, M, Eiriksdottir, G, Gejman, PV, Hall, AS, Hamsten, A, Huikuri, HV, Iribarren, C, Kahonen, M, Kaprio, J, Kathiresan, S, Kiemeney, L, Kocher, T, Launer, LJ, Lehtimaki, T, Melander, O, Mosley, TH, Musk, AW, Nieminen, MS, O'Donnell, CJ, Ohlsson, C, Oostra, B, Palmer, LJ, Raitakari, O, Ridker, PM, Rioux, JD, Rissanen, A, Rivolta, C, Schunkert, H, Shuldiner, AR, Siscovick, DS, Stumvoll, M, Toenjes, A, Tuomilehto, J, van Ommen, G-J, Viikari, J, Heath, AC, Martin, NG, Montgomery, GW, Province, MA, Kayser, M, Arnold, AM, Atwood, LD, Boerwinkle, E, Chanock, SJ, Deloukas, P, Gieger, C, Gronberg, H, Hall, P, Hattersley, AT, Hengstenberg, C, Hoffman, W, Lathrop, GM, Salomaa, V, Schreiber, S, Uda, M, Waterworth, D, Wright, AF, Assimes, TL, Barroso, I, Hofman, A, Mohlke, KL, Boomsma, DI, Caulfield, MJ, Cupples, LA, Erdmann, J, Fox, CS, Gudnason, V, Gyllensten, U, Harris, TB, Hayes, RB, Jarvelin, M-R, Mooser, V, Munroe, PB, Ouwehand, WH, Penninx, BW, Pramstaller, PP, Quertermous, T, Rudan, I, Samani, NJ, Spector, TD, Voelzke, H, Watkins, H, Wilson, JF, Groop, LC, Haritunians, T, Hu, FB, Kaplan, RC, Metspalu, A, North, KE, Schlessinger, D, Wareham, NJ, Hunter, DJ, O'Connell, JR, Strachan, DP, Schadt, H-E, Thorsteinsdottir, U, Peltonen, L, Uitterlinden, AG, Visscher, PM, Chatterjee, N, Loos, RJF, Boehnke, M, McCarthy, MI, Ingelsson, E, Lindgren, CM, Abecasis, GR, Stefansson, K, Frayling, TM, and Hirschhorn, JN
Abstract: Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can ide
Published: 2010

35. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Author: Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, Loos, RJF, Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Hoesel, V, Hottenga, J-J, Johansson, A, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, MF, Myers, RH, Narisu, N, Perry, JRB, Peters, MJ, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Scott, LJ, Timpson, NJ, Tyrer, JP, van Wingerden, S, Watanabe, RM, White, CC, Wiklund, F, Barlassina, C, Chasman, DI, Cooper, MN, Jansson, J-O, Lawrence, RW, Pellikka, N, Prokopenko, I, Shi, J, Thiering, E, Alavere, H, Alibrandi, MTS, Almgren, P, Arnold, AM, Aspelund, T, Atwood, LD, Balkau, B, Balmforth, AJ, Bennett, AJ, Ben-Shlomo, Y, Bergman, RN, Bergmann, S, Biebermann, H, Blakemore, AIF, Boes, T, Bonnycastle, LL, Bornstein, SR, Brown, MJ, Buchanan, TA, Busonero, F, Campbell, H, Cappuccio, FP, Cavalcanti-Proenca, C, Chen, Y-DI, Chen, C-M, Chines, PS, Clarke, R, Coin, L, Connell, J, Day, INM, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Erdos, MR, Eriksson, JG, Facheris, MF, Felix, SB, Fischer-Posovszky, P, Folsom, AR, Friedrich, N, Freimer, NB, Fu, M, Gaget, S, Gejman, PV, Geus, EJC, Gieger, C, Gjesing, AP, Goel, A, Goyette, P, Grallert, H, Graessler, J, Greenawalt, DM, Groves, CJ, Gudnason, V, Guiducci, C, Hartikainen, A-L, Hassanali, N, Hall, AS, Havulinna, AS, Hayward, C, Heath, AC, Hengstenberg, C, Hicks, AA, Hinney, A, Hofman, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Isomaa, B, Jacobs, KB, Jarick, I, Jewell, E, John, U, Jorgensen, T, Jousilahti, P, Jula, A, Kaakinen, M, Kajantie, E, Kaplan, LM, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, JW, Kolcic, I, Koenig, IR, Koskinen, S, Kovacs, P, Kuusisto, J, Kraft, P, Kvaloy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, LJ, Lecoeur, C, Lehtimaeki, T, Lettre, G, Liu, J, Lokki, M-L, Lorentzon, M, Luben, RN, Ludwig, B, Manunta, P, Marek, D, Marre, M, Martin, NG, McArdle, WL, McCarthy, A, McKnight, B, Meitinger, T, Melander, O, Meyre, D, Midthjell, K, Montgomery, GW, Morken, MA, Morris, AP, Mulic, R, Ngwa, JS, Nelis, M, Neville, MJ, Nyholt, DR, O'Donnell, CJ, O'Rahilly, S, Ong, KK, Oostra, B, Pare, G, Parker, AN, Perola, M, Pichler, I, Pietilaeinen, KH, Platou, CGP, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, NW, Ridderstrale, M, Rief, W, Ruokonen, A, Robertson, NR, Rzehak, P, Salomaa, V, Sanders, AR, Sandhu, MS, Sanna, S, Saramies, J, Savolainen, MJ, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, DS, Smit, JH, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Swift, AJ, Tammesoo, M-L, Tardif, J-C, Teder-Laving, M, Teslovich, TM, Thompson, JR, Thomson, B, Toenjes, A, Tuomi, T, van Meurs, JBJ, van Ommen, G-J, Vatin, V, Viikari, J, Visvikis-Siest, S, Vitart, V, Vogel, CIG, Voight, BF, Waite, LL, Wallaschofski, H, Walters, GB, Widen, E, Wiegand, S, Wild, SH, Willemsen, G, Witte, DR, Witteman, JC, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, JP, Farooqi, IS, Hebebrand, J, Huikuri, HV, James, AL, Kaehoenen, M, Levinson, DF, Macciardi, F, Nieminen, MS, Ohlsson, C, Palmer, LJ, Ridker, PM, Stumvoll, M, Beckmann, JS, Boeing, H, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Collins, FS, Cupples, LA, Smith, GD, Erdmann, J, Froguel, P, Greonberg, H, Gyllensten, U, Hall, P, Hansen, T, Harris, TB, Hattersley, AT, Hayes, RB, Heinrich, J, Hu, FB, Hveem, K, Illig, T, Jarvelin, M-R, Kaprio, J, Karpe, F, Khaw, K-T, Kiemeney, LA, Krude, H, Laakso, M, Lawlor, DA, Metspalu, A, Munroe, PB, Ouwehand, WH, Pedersen, O, Penninx, BW, Peters, A, Pramstaller, PP, Quertermous, T, Reinehr, T, Rissanen, A, Rudan, I, Samani, NJ, Schwarz, PEH, Shuldiner, AR, Spector, TD, Tuomilehto, J, Uda, M, Uitterlinden, A, Valle, TT, Wabitsch, M, Waeber, G, Wareham, NJ, Watkins, H, Wilson, JF, Wright, AF, Zillikens, MC, Chatterjee, N, McCarroll, SA, Purcell, S, Schadt, EE, Visscher, PM, Assimes, TL, Borecki, IB, Deloukas, P, Fox, CS, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, Mohlke, KL, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, van Duijn, CM, Wichmann, H-E, Frayling, TM, Thorsteinsdottir, U, Abecasis, GR, Barroso, I, Boehnke, M, Stefansson, K, North, KE, McCarthy, MI, Hirschhorn, JN, Ingelsson, E, and Loos, RJF
Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
Published: 2010

36. Electrocardiographic strain pattern and left ventricular diastolic function in hypertensive patients with left ventricular hypertrophy: the LIFE study.

Author: Palmieri, V, Okin, PM, Bella, JN, Wachtell, K, Gerdts, E, Boman, Kurt, Nieminen, MS, Dahlöf, B, Devereux, RB, Palmieri, V, Okin, PM, Bella, JN, Wachtell, K, Gerdts, E, Boman, Kurt, Nieminen, MS, Dahlöf, B, and Devereux, RB
Abstract: BACKGROUND: Whether the typical electrocardiographic (ECG) strain pattern (Strain, in leads V5 and/or V6), which is associated with left ventricular hypertrophy (LVH) and LV systolic dysfunction, is independently associated with LV diastolic dysfunction is unknown. METHODS: The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study enrolled hypertensive patients with ECG-LVH, of whom 10% underwent Doppler echocardiography. LV diastolic function measures included peak mitral E and A wave velocities and their ratio (E/A); E wave deceleration time (EDT); atrial filling fraction (AFF); and isovolumic relaxation time (IVRT). Normal filling pattern was defined by E/A < 1 with EDT >or= 150 and or=60 ms; abnormal relaxation by E/A < 1 with EDT > 250 ms or IVRT > 100 ms; pseudonormal filling pattern by E/A >or= 1 associated with IVRT > 100 ms or EDT > 250 ms; restrictive pattern by E/A >or= 1 with IVRT < 100 ms and EDT < 250 ms. A combined index of LV systolic-diastolic function was also computed (isovolumic time/ejection time, modified myocardial performance index). Of LIFE echo substudy participants with all needed ECG and Doppler data (n = 791), 110 (14%) had Strain. RESULTS: Strain was associated with male gender, African-American race, diabetes, history of coronary heart disease (CHD), higher systolic blood pressure (BP), LV mass and relative wall thickness, and higher prevalences of echo-LV hypertrophy and wall motion abnormalities, and with slower heart rate (all P < 0.05). Age, diastolic BP and LV ejection fraction were similar in patients with or without Strain. Diastolic parameters, and prevalences of different LV filling patterns, did not differ significantly between patients with versus those without Strain (all P > 0.1), but modified myocardial performance index was higher with Strain (P < 0.05). Findings were consistent in multivariate analyses. The associat
Published: 2006

37. Clarithromycin reduces recurrent cardiovascular events in subjects without periodontitis.

Author: Paju, S, Pussinen, PJ, Sinisalo, J, Mattila, K, Dogan, B, Ahlberg, J, Valtonen, V, Nieminen, MS, Asikainen, Sirkka, Paju, S, Pussinen, PJ, Sinisalo, J, Mattila, K, Dogan, B, Ahlberg, J, Valtonen, V, Nieminen, MS, and Asikainen, Sirkka
Abstract: Inflammation leading to acute coronary syndrome may be triggered by bacteria causing periodontal infection. We investigated if recurrence of cardiovascular events in unstable coronary patients are associated with periodontitis or microbiological/serological markers of it. Periodontitis-related parameters of 141 patients with acute non-Q-wave infarction or unstable angina pectoris, who participated in a double-blind, placebo-controlled study with clarithromycin for 3 months, were adjusted to the occurrence of a recurrent cardiovascular event during a follow-up period (average 519 days). In the age group under 65 years the patients with periodontitis had a univariate odds ratios (OR) 95% confidence intervals (95% CI) of 5.0 (1.02-24.55) for a recurrent cardiovascular event in comparison with patients without periodontitis. Dental status correlated positively with serum lipopolysaccharide concentrations and combined IgG antibody response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. The end point frequency did not differ between clarithromycin and placebo groups in bacterium-positive, seropositive, or periodontitis patients. Fewer end points in clarithromycin group were seen in bacterium-negative, seronegative, edentulous, and non-periodontitis patients. Periodontitis and edentulousness are associated with recurrent cardiovascular events, especially in younger patients. Long-term clarithromycin therapy seems to be beneficial in prevention of recurrent cardiovascular events in non-periodontitis but not in periodontitis patients.
Published: 2006
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38. Electrocardiographic strain pattern and albuminuria additevely predict outcomes in hypertensive patients : The LIFE study

Author: Okin, PM, Wachtell, JK, Nieminen, MS, Lindholm, Lars H, Okin, PM, Wachtell, JK, Nieminen, MS, and Lindholm, Lars H
Published: 2005

39. COMBINED USE OF ELECTROCARDIOGRAM AND ECHOCARDIOGRAM TO BETTER IDENTIFY HYPERTENSIVE PATIENTS AT HIGH RISK FOR HEART FAILURE: 4C.06

Author: Gerdts, E, primary, Okin, P, additional, Wachtell, K, additional, Boman, K, additional, Nieminen, MS, additional, Dahlöf, B, additional, and Devereux, RB, additional
Published: 2010
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40. F176 Comparison of the effects of transdermal and oral HRT on ambulatory blood pressure in postmenopausal women

Author: Paakkari, I, primary, Hasselblatt, R, additional, Nieminen, MS, additional, Cacciatore, B, additional, Toivonen, J, additional, Tikkanen, MJ, additional, and Ylikorkala, O, additional
Published: 1996
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41. Losartan versus atenolol-based antihypertensive treatment reduces cardiovascular events especially well in elderly patients: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study.

Author: Ruwald AC, Westergaard B, Sehestedt T, Kjeldsen SE, Lindholm LH, Wachtell K, Devereux RB, Ibsen H, Nieminen MS, Dahlöf B, and Olsen MH
Published: 2012
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42. The COACH risk engine: a multistate model for predicting survival and hospitalization in patients with heart failure.

Author: Postmus D, van Veldhuisen DJ, Jaarsma T, Luttik ML, Lassus J, Mebazaa A, Nieminen MS, Harjola VP, Lewsey J, Buskens E, and Hillege HL
Published: 2012

43. Changes in subclinical organ damage vs. in Framingham risk score for assessing cardiovascular risk reduction during continued antihypertensive treatment: a LIFE substudy.

Author: Olsen MH, Wachtell K, Ibsen H, Lindholm L, Kjeldsen SE, Omvik P, Nieminen MS, Dahlöf B, Okin PM, Devereux RB, Olsen, Michael H, Wachtell, Kristian, Ibsen, Hans, Lindholm, Lars, Kjeldsen, Sverre E, Omvik, Per, Nieminen, Markku S, Dahlöf, Björn, Okin, Peter M, and Devereux, Richard B
Published: 2011
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44. Beneficial association of [beta]-blocker therapy on recovery from severe acute heart failure treatment: data from the Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support trial.

Author: Böhm M, Link A, Cai D, Nieminen MS, Filippatos GS, Salem R, Cohen Solal A, Huang B, Padley RJ, Kivikko M, and Mebazaa A
Published: 2011
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45. Oral levosimendan improves filling pressure and systolic function during long-term treatment.

Author: Jalanko M, Kivikko M, Harjola VP, Nieminen MS, and Laine M
Published: 2011

46. Serial assessment of the electrocardiographic strain pattern for prediction of new-onset heart failure during antihypertensive treatment: the LIFE study.

Author: Okin PM, Oikarinen L, Viitasalo M, Toivonen L, Kjeldsen SE, Nieminen MS, Edelman JM, Dahlöf B, Devereux RB, and LIFE Study Investigators
Published: 2011
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47. Relationship of left atrial enlargement to persistence or development of ECG left ventricular hypertrophy in hypertensive patients: implications for the development of new atrial fibrillation.

Author: Okin PM, Gerdts E, Wachtell K, Oikarinen L, Nieminen MS, Dahlöf B, Devereux RB, Okin, Peter M, Gerdts, Eva, Wachtell, Kristian, Oikarinen, Lasse, Nieminen, Markku S, Dahlöf, Björn, and Devereux, Richard B
Published: 2010
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48. In-treatment midwall and endocardial fractional shortening predict cardiovascular outcome in hypertensive patients with preserved baseline systolic ventricular function: the Losartan Intervention For Endpoint reduction study.

Author: Wachtell K, Gerdts E, Palmieri V, Olsen MH, Nieminen MS, Papademetriou V, Boman K, Dahlöf B, Aurigemma GP, Rokkedal JE, Devereux RB, Wachtell, Kristian, Gerdts, Eva, Palmieri, Vittorio, Olsen, Michael H, Nieminen, Markku S, Papademetriou, Vasilios, Boman, Kurt, Dahlöf, Björn, and Aurigemma, Gerard P
Published: 2010
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49. Eight-year safety follow-up of coronary artery disease patients after local intracoronary VEGF gene transfer.

Author: Hedman, M., Muona, K., Hedman, A., Kivelä, A., Syvänne, M., Eränen, J., Rantala, A., Stjernvall, J., Nieminen, MS, Hartikainen, J., and Ylä-Herttuala, S.
Subjects: HEART diseases, CANCER patients, THERAPEUTICS, GENETIC transformation, DIABETIC acidosis
Abstract: Vascular endothelial growth factor (VEGF) has been shown to stimulate angiogenesis and myocardial perfusion. The short-term safety of VEGF gene therapy is excellent. However, there are only limited results regarding the long-term effects. The Kuopio Angiogenesis Trial (KAT) studied the efficiency and short-term safety of the local VEGF-A165 gene transfer in 103 patients with coronary artery disease. Three patient groups received either VEGF as an adenoviral (n=37), or as a plasmid/liposome vector (n=28), or as a placebo (n=38), during coronary angioplasty and stenting (percutaneous coronary intervention, PCI)AQ1. The aim of this study was to examine the long-term effects and safety of VEGF gene therapy. Patients were interviewed by telephone or with a questionnaire on their current status of health, coronary and other cardiovascular events and symptoms, working ability, exercise tolerance, other diseases, such as cancer and diabetes, as well as their personal experience of the treatment. Causes of death were clarified from hospital records. The total follow-up time was 8.1 years (range 6.9–9.7 years). Overall 82% of the patients were reached across the study. Eight (7.5%) of the patients died during the follow-up, but there was no significant difference in mortality between the groups (3/32 vs 2/26 vs 3/31 VEGF-adenovirus vs VEGF-plasmid/liposome vs placebo, respectively; P=0.88). The incidence of major adverse cardiovascular events (MACEs) (10 vs 11 vs 15; P=0.85), cancer (1 vs 4 vs 2; P=0.38) or diabetes (2 vs 2 vs 2; P=0.97) did not differ between the groups. Local intracoronary VEGF gene transfer is safe and does not increase the risk of MACE, arrhythmias, cancer, diabetes or other diseases.Gene Therapy (2009) 16, 629–634; doi:10.1038/gt.2009.4; published online 12 February 2009 [ABSTRACT FROM AUTHOR]
Published: 2009
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50. Prognostic value of changes in the electrocardiographic strain pattern during antihypertensive treatment: the Losartan Intervention for End-Point Reduction in Hypertension Study (LIFE)

Author: Okin PM, Oikarinen L, Viitasalo M, Toivonen L, Kjeldsen SE, Nieminen MS, Edelman JM, Dahlöf B, Devereux RB, and LIFE Study Investigators
Published: 2009
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